Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Orlo H Clark x
  • Refine by access: All content x
Clear All Modify Search
Michael W Yeh
Search for other papers by Michael W Yeh in
Google Scholar
PubMed
Close
,
Jean-Philippe Rougier
Search for other papers by Jean-Philippe Rougier in
Google Scholar
PubMed
Close
,
Jin-Woo Park
Search for other papers by Jin-Woo Park in
Google Scholar
PubMed
Close
,
Quan-Yang Duh
Search for other papers by Quan-Yang Duh in
Google Scholar
PubMed
Close
,
Mariwil Wong
Search for other papers by Mariwil Wong in
Google Scholar
PubMed
Close
,
Zena Werb
Search for other papers by Zena Werb in
Google Scholar
PubMed
Close
, and
Orlo H Clark
Search for other papers by Orlo H Clark in
Google Scholar
PubMed
Close

Mechanisms of invasion in thyroid cancer remain poorly understood. We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs). Papillary and follicular carcinoma cell lines were treated with EGF, the EGFR tyrosine kinase inhibitor AG1478, and the MMP inhibitors GM-6001 and Col-3. Flow cytometry was used to detect EGFR. In vitro invasion assays, gelatin zymography, and quantitative reverse transcription-PCR were used to assess the changes in invasive behavior and MMP expression and activation. All cell lines were found to overexpress functional EGFR. EGF stimulated invasion by thyroid cancer cells up to sevenfold (P < 0.0001), a process that was antagonized completely by AG1478 and Col-3, partially by GM-6001, but not by the serine protease inhibitor aprotinin. EGF upregulated expression of MMP-9 (2.64- to 8.89-fold, P < 0.0001) and membrane type-1 MMP (MT1-MMP, 1.97- to 2.67-fold, P < 0.0001). This effect was blocked completely by AG1478 and partially by Col-3. The activation of MMP-2 paralleled MT1-MMP expression. We demonstrate that MMPs are critical effectors of invasion in the papillary and follicular thyroid cancer cell lines studied. Invasion is regulated by signaling through EGFR, an effect mediated by augmentation of gelatinase expression and activation. MMP inhibitors and growth factor antagonists may be effective tumoristatic agents for the treatment of aggressive thyroid carcinomas.

Free access
Goswin Y Meyer-Rochow Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Goswin Y Meyer-Rochow in
Google Scholar
PubMed
Close
,
Nicole E Jackson Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Nicole E Jackson in
Google Scholar
PubMed
Close
,
John V Conaglen Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by John V Conaglen in
Google Scholar
PubMed
Close
,
Denis E Whittle Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Denis E Whittle in
Google Scholar
PubMed
Close
,
Muthusamy Kunnimalaiyaan Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Muthusamy Kunnimalaiyaan in
Google Scholar
PubMed
Close
,
Herbert Chen Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Herbert Chen in
Google Scholar
PubMed
Close
,
Gunnar Westin Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Gunnar Westin in
Google Scholar
PubMed
Close
,
Johanna Sandgren Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Johanna Sandgren in
Google Scholar
PubMed
Close
,
Peter Stålberg Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Peter Stålberg in
Google Scholar
PubMed
Close
,
Elham Khanafshar Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Elham Khanafshar in
Google Scholar
PubMed
Close
,
Daniel Shibru Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Daniel Shibru in
Google Scholar
PubMed
Close
,
Quan-Yang Duh Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Quan-Yang Duh in
Google Scholar
PubMed
Close
,
Orlo H Clark Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Orlo H Clark in
Google Scholar
PubMed
Close
,
Electron Kebebew Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Electron Kebebew in
Google Scholar
PubMed
Close
,
Anthony J Gill Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Anthony J Gill in
Google Scholar
PubMed
Close
,
Rory Clifton-Bligh Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Rory Clifton-Bligh in
Google Scholar
PubMed
Close
,
Bruce G Robinson Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Bruce G Robinson in
Google Scholar
PubMed
Close
,
Diana E Benn Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Diana E Benn in
Google Scholar
PubMed
Close
, and
Stan B Sidhu Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of
Cancer Genetics, Endocrine and Oncology Surgery, Endocrinology, Anatomical Pathology, Faculty of Medicine, Surgery, Endocrinology, Endocrine Surgery Research Laboratories, Department of Surgical Sciences, Departments of Surgery and Pathology, Endocrine Oncology Section, Hormones and Cancer Group, Kolling Institute of Medical Research, Departments of

Search for other papers by Stan B Sidhu in
Google Scholar
PubMed
Close

MicroRNAs (miRNAs) are small RNAs (∼22 bp) that post-transcriptionally regulate protein expression and are found to be differentially expressed in a number of human cancers. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. We performed miRNA microarray expression profiling on a cohort of 12 benign and 12 malignant pheochromocytomas and identified a number of differentially expressed miRNAs. These results were validated in a separate cohort of ten benign and ten malignant samples using real-time quantitative RT-PCR; benign samples had a minimum follow-up of at least 2 years. It was found that IGF2 as well as its intronic miR-483-5p was over-expressed, while miR-15a and miR-16 were under-expressed in malignant tumours compared with benign tumours. These miRNAs were found to be diagnostic and prognostic markers for malignant pheochromocytoma. The functional role of miR-15a and miR-16 was investigated in vitro in the rat PC12 pheochromocytoma cell line, and these miRNAs were found to regulate cell proliferation via their effect on cyclin D1 and apoptosis. These data indicate that miRNAs play a pivotal role in the biology of malignant pheochromocytoma, and represent an important class of diagnostic and prognostic biomarkers and therapeutic targets warranting further investigation.

Free access