Search Results

You are looking at 1 - 9 of 9 items for

  • Author: Massimo Santoro x
  • Refine by access: All content x
Clear All Modify Search
Francesca Carlomagno F Carlomagno, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy

Search for other papers by Francesca Carlomagno in
Google Scholar
PubMed
Close
,
Marialuisa Moccia M Moccia, Istituto di Endocrinologia e Oncologia Sperimentale , Consiglio Nazionale delle Ricerche, Napoli, Italy

Search for other papers by Marialuisa Moccia in
Google Scholar
PubMed
Close
,
Giorgia Federico G Federico, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy

Search for other papers by Giorgia Federico in
Google Scholar
PubMed
Close
, and
Massimo Santoro M Santoro, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy

Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close

The RET receptor tyrosine kinase is physiologically stimulated by growth factors belonging to the glial cell line-derived neurotrophic factor (GDNF) family (GFLs) and by the growth differentiation factor-15 (GDF15) cytokine. RET plays a critical role in normal development as well as in various human tumors and developmental disorders. This review focuses on mechanisms of RET signaling and their alterations in human diseases.

Restricted access
Francesca Carlomagno
Search for other papers by Francesca Carlomagno in
Google Scholar
PubMed
Close
,
Teresa Guida
Search for other papers by Teresa Guida in
Google Scholar
PubMed
Close
,
Suresh Anaganti
Search for other papers by Suresh Anaganti in
Google Scholar
PubMed
Close
,
Livia Provitera
Search for other papers by Livia Provitera in
Google Scholar
PubMed
Close
,
Svend Kjaer Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Structural Biology Laboratory, Cancer Discovery, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Svend Kjaer in
Google Scholar
PubMed
Close
,
Neil Q McDonald Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Structural Biology Laboratory, Cancer Discovery, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Neil Q McDonald in
Google Scholar
PubMed
Close
,
Anderson J Ryan Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Structural Biology Laboratory, Cancer Discovery, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Anderson J Ryan in
Google Scholar
PubMed
Close
, and
Massimo Santoro
Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close

ZD6474 (vandetanib, Zactima, Astra Zeneca) is an anilinoquinazoline used to target the receptor tyrosine kinase RET in familial and sporadic thyroid carcinoma (IC50: 100 nM). The aim of this study was to identify molecular determinants of RET sensitivity to ZD6474. Here, we show that mutation of RET tyrosine 806 to cysteine (Y806C) induced RET kinase resistance to ZD6474 (IC50: 933 nM). Y806 maps close to the gate-keeper position at the RET kinase nucleotide-binding pocket. Although tyrosine 806 is a RET auto-phosphorylation site, its substitution to phenylalanine (Y806F) did not markedly affect RET susceptibility to ZD6474 (IC50: 87 nM), suggesting that phosphorylation of Y806 is not required for compound binding. Accordingly, the introduction of a phosphomimetic residue (Y806E) also caused resistance to ZD6474, albeit of a lesser degree (IC50: 512 nM) than the cysteine mutation. Y806C/E RET mutants were also resistant to ZD6474 with respect to intracellular signalling and activation of an AP1-responsive promoter. We conclude that Y806 is a molecular determinant of RET sensitivity to ZD6474. Y806C is a natural RET mutation identified in a patient affected by multiple endocrine neoplasia type 2B. Based on its rare occurrence, it is unlikely that Y806C will be a frequent cause of refractoriness to ZD6474; however, it may be envisaged that mutations at this site can mediate secondary resistance formation in patients treated with the compound.

Free access
Ornella Affinito Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy

Search for other papers by Ornella Affinito in
Google Scholar
PubMed
Close
,
Paolo Salerno Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy

Search for other papers by Paolo Salerno in
Google Scholar
PubMed
Close
,
Alfonso D’Alessio Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy

Search for other papers by Alfonso D’Alessio in
Google Scholar
PubMed
Close
,
Mariella Cuomo Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy

Search for other papers by Mariella Cuomo in
Google Scholar
PubMed
Close
,
Ermanno Florio Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy

Search for other papers by Ermanno Florio in
Google Scholar
PubMed
Close
,
Francesca Carlomagno Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Napoli, Italy

Search for other papers by Francesca Carlomagno in
Google Scholar
PubMed
Close
,
Agnese Proietti Division of Anatomical Pathology, University Hospital of Pisa (AO-UP), Pisa, Italy

Search for other papers by Agnese Proietti in
Google Scholar
PubMed
Close
,
Riccardo Giannini Department of Surgical, Medical, Molecular Pathology and Critical Area (Anatomical Pathology Section), University of Pisa, Pisa, Italy

Search for other papers by Riccardo Giannini in
Google Scholar
PubMed
Close
,
Fulvio Basolo Department of Surgical, Medical, Molecular Pathology and Critical Area (Anatomical Pathology Section), University of Pisa, Pisa, Italy

Search for other papers by Fulvio Basolo in
Google Scholar
PubMed
Close
,
Lorenzo Chiariotti Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Napoli, Italy

Search for other papers by Lorenzo Chiariotti in
Google Scholar
PubMed
Close
,
Sergio Cocozza Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy

Search for other papers by Sergio Cocozza in
Google Scholar
PubMed
Close
, and
Massimo Santoro Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Federico II, Napoli, Italy

Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close

Molecular differentiation between benign (follicular thyroid adenoma (FTA)) and malignant (follicular thyroid carcinoma (FTC)) thyroid neoplasms is challenging. Here, we explored the genome-wide DNA methylation profile of FTA (n.10) and FTC (n.11) compared to normal thyroid (NT) (n.7) tissues. FTC featured 3564 differentially methylated CpGs (DMCpG), most (84%) of them hypermethylated, with respect to normal controls. At the principal component analysis (PCA), the methylation profile of FTA occupied an intermediate position between FTC and normal tissue. A large fraction (n. 2385) of FTC-associated DMCpG was related (intragenic or within 1500 bp from the transcription start site) to annotated genes (n. 1786). FTC-hypermethylated genes were enriched for targets of the Polycomb transcriptional repressor complex and the specific histone H3 marks (H3K4me2/me3-H3K27me3) found in chromatin domains known as ‘bivalent’. Transcriptome profiling by RNAseq showed that 7.9% of the DMCpGs-associated genes were differentially expressed in FTC compared to NT, suggesting that altered DNA methylation may contribute to their altered expression. Overall, this study suggests that perturbed DNA methylation, in particular hypermethylation, is a component of the molecular mechanisms leading to the formation of FTC and that DNA methylation profiling may help differentiating FTCs from their benign counterpart.

Free access
Donata Vitagliano
Search for other papers by Donata Vitagliano in
Google Scholar
PubMed
Close
,
Valentina De Falco
Search for other papers by Valentina De Falco in
Google Scholar
PubMed
Close
,
Anna Tamburrino
Search for other papers by Anna Tamburrino in
Google Scholar
PubMed
Close
,
Sabrina Coluzzi
Search for other papers by Sabrina Coluzzi in
Google Scholar
PubMed
Close
,
Giancarlo Troncone Dipartimento di Biologia e Patologia Cellulare e Molecolare, Dipartimento di Scienze Biomorfologiche e Funzionali, Istituto Nazionale dei Tumori di Napoli, Division of Medical Oncology, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Department of Medicine and Human Oncology and Pathogenesis Program, Cancer Discovery, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università Federico II, Via S. Pansini 5, 80131 Napoli, Italy

Search for other papers by Giancarlo Troncone in
Google Scholar
PubMed
Close
,
Gennaro Chiappetta Dipartimento di Biologia e Patologia Cellulare e Molecolare, Dipartimento di Scienze Biomorfologiche e Funzionali, Istituto Nazionale dei Tumori di Napoli, Division of Medical Oncology, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Department of Medicine and Human Oncology and Pathogenesis Program, Cancer Discovery, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università Federico II, Via S. Pansini 5, 80131 Napoli, Italy

Search for other papers by Gennaro Chiappetta in
Google Scholar
PubMed
Close
,
Fortunato Ciardiello Dipartimento di Biologia e Patologia Cellulare e Molecolare, Dipartimento di Scienze Biomorfologiche e Funzionali, Istituto Nazionale dei Tumori di Napoli, Division of Medical Oncology, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Department of Medicine and Human Oncology and Pathogenesis Program, Cancer Discovery, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università Federico II, Via S. Pansini 5, 80131 Napoli, Italy

Search for other papers by Fortunato Ciardiello in
Google Scholar
PubMed
Close
,
Giampaolo Tortora Dipartimento di Biologia e Patologia Cellulare e Molecolare, Dipartimento di Scienze Biomorfologiche e Funzionali, Istituto Nazionale dei Tumori di Napoli, Division of Medical Oncology, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Department of Medicine and Human Oncology and Pathogenesis Program, Cancer Discovery, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università Federico II, Via S. Pansini 5, 80131 Napoli, Italy

Search for other papers by Giampaolo Tortora in
Google Scholar
PubMed
Close
,
James A Fagin Dipartimento di Biologia e Patologia Cellulare e Molecolare, Dipartimento di Scienze Biomorfologiche e Funzionali, Istituto Nazionale dei Tumori di Napoli, Division of Medical Oncology, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Department of Medicine and Human Oncology and Pathogenesis Program, Cancer Discovery, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università Federico II, Via S. Pansini 5, 80131 Napoli, Italy

Search for other papers by James A Fagin in
Google Scholar
PubMed
Close
,
Anderson J Ryan Dipartimento di Biologia e Patologia Cellulare e Molecolare, Dipartimento di Scienze Biomorfologiche e Funzionali, Istituto Nazionale dei Tumori di Napoli, Division of Medical Oncology, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Department of Medicine and Human Oncology and Pathogenesis Program, Cancer Discovery, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università Federico II, Via S. Pansini 5, 80131 Napoli, Italy

Search for other papers by Anderson J Ryan in
Google Scholar
PubMed
Close
,
Francesca Carlomagno
Search for other papers by Francesca Carlomagno in
Google Scholar
PubMed
Close
, and
Massimo Santoro
Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close

Oncogenic conversion of the RET tyrosine kinase is a frequent feature of medullary thyroid carcinoma (MTC). ZD6474 (vandetanib) is an ATP-competitive inhibitor of RET, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptors kinases. In this study, we have studied ZD6474 mechanism of action in TT and MZ-CRC-1 human MTC cell lines, carrying cysteine 634 to tryptophan (C634W) and methionine 918 to threonine (M918T) RET mutation respectively. ZD6474 blunted MTC cell proliferation and RET, Shc and p44/p42 mitogen-activated protein kinase (MAPK) phosphorylation. Single receptor knockdown by RNA interference showed that MTC cells depended on RET for proliferation. Adoptive expression of the ZD6474-resistant V804M RET mutant rescued proliferation of TT cells under ZD6474 treatment, showing that RET is a key ZD6474 target in these MTC cells. Upon RET inhibition, adoptive stimulation of EGFR partially rescued TT cell proliferation, MAPK signaling, and expression of cell-cycle-related genes. This suggests that simultaneous inhibition of RET and EGFR by ZD6474 may overcome the risk of MTC cells to escape from RET blockade through compensatory over-activation of EGFR.

Free access
Roberto Bellelli Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Roberto Bellelli in
Google Scholar
PubMed
Close
,
Maria Domenica Castellone Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Maria Domenica Castellone in
Google Scholar
PubMed
Close
,
Ginesa Garcia-Rostan Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Ginesa Garcia-Rostan in
Google Scholar
PubMed
Close
,
Clara Ugolini Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Clara Ugolini in
Google Scholar
PubMed
Close
,
Carmelo Nucera Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Carmelo Nucera in
Google Scholar
PubMed
Close
,
Peter M Sadow Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Peter M Sadow in
Google Scholar
PubMed
Close
,
Tito Claudio Nappi Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Tito Claudio Nappi in
Google Scholar
PubMed
Close
,
Paolo Salerno Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Paolo Salerno in
Google Scholar
PubMed
Close
,
Maria Carmela Cantisani Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Maria Carmela Cantisani in
Google Scholar
PubMed
Close
,
Fulvio Basolo Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Fulvio Basolo in
Google Scholar
PubMed
Close
,
Tomas Alvarez Gago Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Tomas Alvarez Gago in
Google Scholar
PubMed
Close
,
Giuliana Salvatore Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Giuliana Salvatore in
Google Scholar
PubMed
Close
, and
Massimo Santoro Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale ‘G. Salvatore’, Institute of Biology and Molecular Genetics, Department of Surgery, Human Thyroid Cancers Preclinical and Translational Research Program, Department of Pathology, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, ‘L. Califano’, Universita' Federico II, Napoli, Italy

Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close

Anaplastic thyroid carcinoma (ATC) is a very aggressive thyroid cancer. forkhead box protein M1 (FOXM1) is a member of the forkhead box family of transcription factors involved in control of cell proliferation, chromosomal stability, angiogenesis, and invasion. Here, we show that FOXM1 is significantly increased in ATCs compared with normal thyroid, well-differentiated thyroid carcinomas (papillary and/or follicular), and poorly differentiated thyroid carcinomas (P=0.000002). Upregulation of FOXM1 levels in ATC cells was mechanistically linked to loss-of-function of p53 and to the hyperactivation of the phosphatidylinositol-3-kinase/AKT/FOXO3a pathway. Knockdown of FOXM1 by RNA interference inhibited cell proliferation by arresting cells in G2/M and reduced cell invasion and motility. This phenotype was associated with decreased expression of FOXM1 target genes, like cyclin B1 (CCNB1), polo-like kinase 1 (PLK1), Aurora B (AURKB), S-phase kinase-associated protein 2 (SKP2), and plasminogen activator, urokinase: uPA (PLAU). Pharmacological inhibition of FOXM1 in an orthotopic mouse model of ATC reduced tumor burden and metastasization. All together, these findings suggest that FOXM1 represents an important player in thyroid cancer progression to the anaplastic phenotype and a potential therapeutic target for this fatal cancer.

Free access
Katrin-Janine Heiliger
Search for other papers by Katrin-Janine Heiliger in
Google Scholar
PubMed
Close
,
Julia Hess
Search for other papers by Julia Hess in
Google Scholar
PubMed
Close
,
Donata Vitagliano Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Donata Vitagliano in
Google Scholar
PubMed
Close
,
Paolo Salerno Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Paolo Salerno in
Google Scholar
PubMed
Close
,
Herbert Braselmann
Search for other papers by Herbert Braselmann in
Google Scholar
PubMed
Close
,
Giuliana Salvatore Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Giuliana Salvatore in
Google Scholar
PubMed
Close
,
Clara Ugolini Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Clara Ugolini in
Google Scholar
PubMed
Close
,
Isolde Summerer Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Isolde Summerer in
Google Scholar
PubMed
Close
,
Tatjana Bogdanova Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Tatjana Bogdanova in
Google Scholar
PubMed
Close
,
Kristian Unger Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Kristian Unger in
Google Scholar
PubMed
Close
,
Gerry Thomas Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Gerry Thomas in
Google Scholar
PubMed
Close
,
Massimo Santoro Research Unit of Radiation Cytogenetics, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Division of Pathology, Institute of Radiation Biology, Institute of Endocrinology and Metabolism, Department of Surgery and Cancer, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany

Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close
, and
Horst Zitzelsberger
Search for other papers by Horst Zitzelsberger in
Google Scholar
PubMed
Close

For an identification of novel candidate genes in thyroid tumourigenesis, we have investigated gene copy number changes in a Trk-T1 transgenic mouse model of thyroid neoplasia. For this aim, 30 thyroid tumours from Trk-T1 transgenics were investigated by comparative genomic hybridisation. Recurrent gene copy number alterations were identified and genes located in the altered chromosomal regions were analysed by Gene Ontology term enrichment analysis in order to reveal gene functions potentially associated with thyroid tumourigenesis. In thyroid neoplasms from Trk-T1 mice, a recurrent gain on chromosomal bands 1C4–E2.3 (10.0% of cases), and losses on 3H1–H3 (13.3%), 4D2.3–E2 (43.3%) and 14E4–E5 (6.7%) were identified. The genes Twist2, Ptma, Pde6d, Bmpr1b, Pdlim5, Unc5c, Srm, Trp73, Ythdf2, Taf12 and Slitrk5 are located in these chromosomal bands. Copy number changes of these genes were studied by fluorescence in situ hybridisation on 30 human papillary thyroid carcinoma (PTC) samples and altered gene expression was studied by qRT-PCR analyses in 67 human PTC. Copy number gains were detected in 83% of cases for TWIST2 and in 100% of cases for PTMA and PDE6D. DNA losses of SLITRK1 and SLITRK5 were observed in 21% of cases and of SLITRK6 in 16% of cases. Gene expression was significantly up-regulated for UNC5C and TP73 and significantly down-regulated for SLITRK5 in tumours compared with normal tissue. In conclusion, a global genomic copy number analysis of thyroid tumours from Trk-T1 transgenic mice revealed a number of novel gene alterations in thyroid tumourigenesis that are also prevalent in human PTCs.

Free access
Monica Fedele Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Monica Fedele in
Google Scholar
PubMed
Close
,
Dario Palmieri Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Dario Palmieri in
Google Scholar
PubMed
Close
,
Gennaro Chiappetta Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Gennaro Chiappetta in
Google Scholar
PubMed
Close
,
Rosa Pasquinelli Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Rosa Pasquinelli in
Google Scholar
PubMed
Close
,
Ivana De Martino Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Ivana De Martino in
Google Scholar
PubMed
Close
,
Claudio Arra Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Claudio Arra in
Google Scholar
PubMed
Close
,
Giuseppe Palma Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Giuseppe Palma in
Google Scholar
PubMed
Close
,
Teresa Valentino Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Teresa Valentino in
Google Scholar
PubMed
Close
,
Giovanna M Pierantoni Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Giovanna M Pierantoni in
Google Scholar
PubMed
Close
,
Giuseppe Viglietto Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Giuseppe Viglietto in
Google Scholar
PubMed
Close
,
Jay L Rothstein Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Jay L Rothstein in
Google Scholar
PubMed
Close
,
Massimo Santoro Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close
, and
Alfredo Fusco Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto dei Tumori di Napoli Fondazione ‘G. Pascale’, Dipartimento di Medicina Sperimentale e Clinica, Inflammation Research, NOGEC (Naples Oncogenomic Center)-Ceinge, Via S. Pansini 5, 80131 Naples, Italy

Search for other papers by Alfredo Fusco in
Google Scholar
PubMed
Close

Impairment of the p27kip1 function, caused by a drastic reduction of its expression or cytoplasmic mislocalization, has been frequently observed in thyroid carcinomas. To understand the role of p27kip1 impairment in thyroid carcinogenesis, we investigated the consequences of the loss of p27kip1 expression in the context of a mouse modeling of papillary thyroid cancer, expressing the TRK-T1 oncogene under the transcriptional control of thyroglobulin promoter. We found that double mutant mice homozygous for a p27 kip1 null allele (TRK-T1/p27 −/− ) display a higher incidence of papillary thyroid carcinomas, with a shorter latency period and increased proliferation index, compared with p27 kip1 wild-type compounds (TRK-T1/p27 +/+ ). Consistently, double mutant mice heterozygous for a p27 kip1 null allele (TRK-T1/p27 +/− ) show an incidence of thyroid carcinomas that is intermediate between TRK-T1/p27 −/− and TRK-T1/p27 +/+ mice. Therefore, our findings suggest a dose-dependent role of p27 kip1 function in papillary thyroid cancer development.

Free access
Maria Rosaria Rusciano Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Maria Rosaria Rusciano in
Google Scholar
PubMed
Close
,
Marcella Salzano Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Marcella Salzano in
Google Scholar
PubMed
Close
,
Sara Monaco Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Sara Monaco in
Google Scholar
PubMed
Close
,
Maria Rosaria Sapio Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Maria Rosaria Sapio in
Google Scholar
PubMed
Close
,
Maddalena Illario Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Maddalena Illario in
Google Scholar
PubMed
Close
,
Valentina De Falco Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Valentina De Falco in
Google Scholar
PubMed
Close
,
Massimo Santoro Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close
,
Pietro Campiglia Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Pietro Campiglia in
Google Scholar
PubMed
Close
,
Lucio Pastore Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy
Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Lucio Pastore in
Google Scholar
PubMed
Close
,
Gianfranco Fenzi Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Gianfranco Fenzi in
Google Scholar
PubMed
Close
,
Guido Rossi Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy
Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Guido Rossi in
Google Scholar
PubMed
Close
, and
Mario Vitale Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy
Department of Biologia e Patologia Cellulare e Molecolare, Department of Endocrinologia ed Oncologia Molecolare e Clinica, Department of Scienze Farmaceutiche, Department of Biochimica e Biotecnologie Mediche, CEINGE-Biotecnologie Avanzate, CISI, Facoltà di Medicina, Università Federico II, Naples, Italy

Search for other papers by Mario Vitale in
Google Scholar
PubMed
Close

RET/papillary thyroid carcinoma (PTC), TRK-T, or activating mutations of Ras and BRaf are frequent genetic alterations in PTC, all leading to the activation of the extracellular-regulated kinase (Erk) cascade. The aim of this study was to investigate the role of calmodulin-dependent kinase II (CaMKII) in the signal transduction leading to Erk activation in PTC cells. In normal thyroid cells, CaMKII and Erk were in the inactive form in the absence of stimulation. In primary PTC cultures and in PTC cell lines harboring the oncogenes RET/PTC-1 or BRafV600E, CaMKII was active also in the absence of any stimulation. Inhibition of calmodulin or phospholipase C (PLC) attenuated the level of CaMKII activation. Expression of recombinant RET/PTC-3, BRafV600E, or RasV12 induced CaMKII activation. Inhibition of CaMKII attenuated Erk activation and DNA synthesis in thyroid papillary carcinoma (TPC-1), a cell line harboring RET/PTC-1, suggesting that CaMKII is a component of the Erk signal cascade in this cell line. In conclusion, PTCs contain an active PLC/Ca2+/calmodulin-dependent signal inducing constitutive activation of CaMKII. This kinase is activated by BRafV600E, oncogenic Ras, and by RET/PTC. CaMKII participates to the activation of the Erk pathway by oncogenic Ras and RET/PTC and contributes to their signal output, thus modulating tumor cell proliferation.

Free access
Lilja E Laatikainen Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Lilja E Laatikainen in
Google Scholar
PubMed
Close
,
Maria D Castellone Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Maria D Castellone in
Google Scholar
PubMed
Close
,
Aline Hebrant Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Aline Hebrant in
Google Scholar
PubMed
Close
,
Candice Hoste Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Candice Hoste in
Google Scholar
PubMed
Close
,
Maria C Cantisani Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Maria C Cantisani in
Google Scholar
PubMed
Close
,
Juha P Laurila Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Juha P Laurila in
Google Scholar
PubMed
Close
,
Giuliana Salvatore Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Giuliana Salvatore in
Google Scholar
PubMed
Close
,
Paolo Salerno Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Paolo Salerno in
Google Scholar
PubMed
Close
,
Fulvio Basolo Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Fulvio Basolo in
Google Scholar
PubMed
Close
,
Johnny Näsman Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Johnny Näsman in
Google Scholar
PubMed
Close
,
Jacques E Dumont Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Jacques E Dumont in
Google Scholar
PubMed
Close
,
Massimo Santoro Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Massimo Santoro in
Google Scholar
PubMed
Close
, and
Mikko O Laukkanen Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland
Cellular Therapy Group, Institute of Experimental Endocrinology and Oncology (CNR), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Dipartimento di Chirurgia, Åbo Akademi University, Fondazione IRCCS SDN, Medicity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland

Search for other papers by Mikko O Laukkanen in
Google Scholar
PubMed
Close

Reactive oxygen species, specifically hydrogen peroxide (H2O2), have a significant role in hormone production in thyroid tissue. Although recent studies have demonstrated that dual oxidases are responsible for the H2O2 synthesis needed in thyroid hormone production, our data suggest a pivotal role for superoxide dismutase 3 (SOD3) as a major H2O2-producing enzyme. According to our results, Sod3 is highly expressed in normal thyroid, and becomes even more abundant in rat goiter models. We showed TSH-stimulated expression of Sod3 via phospholipase C–Ca2+ and cAMP–protein kinase A, a pathway that might be disrupted in thyroid cancer. In line with this finding, we demonstrated an oncogene-dependent decrease in Sod3 mRNA expression synthesis in thyroid cancer cell models that corresponded to a similar decrease in clinical patient samples, suggesting that SOD3 could be used as a differentiation marker in thyroid cancer. Finally, the functional analysis in thyroid models indicated a moderate role for SOD3 in regulating normal thyroid cell proliferation being in line with our previous observations.

Free access