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Pharmacology Drug Development and Therapeutics
Turku Center for Disease Modeling Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
Functional Foods Forum University of Turku, Turku, Finland
Department of Laboratory Medicine MAS University Hospital, Lund University, Malmö, Sweden
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Pharmacology Drug Development and Therapeutics
Turku Center for Disease Modeling Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
Functional Foods Forum University of Turku, Turku, Finland
Department of Laboratory Medicine MAS University Hospital, Lund University, Malmö, Sweden
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Pharmacology Drug Development and Therapeutics
Turku Center for Disease Modeling Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
Functional Foods Forum University of Turku, Turku, Finland
Department of Laboratory Medicine MAS University Hospital, Lund University, Malmö, Sweden
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Pharmacology Drug Development and Therapeutics
Turku Center for Disease Modeling Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
Functional Foods Forum University of Turku, Turku, Finland
Department of Laboratory Medicine MAS University Hospital, Lund University, Malmö, Sweden
Departments of Cell Biology and Anatomy
Pharmacology Drug Development and Therapeutics
Turku Center for Disease Modeling Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
Functional Foods Forum University of Turku, Turku, Finland
Department of Laboratory Medicine MAS University Hospital, Lund University, Malmö, Sweden
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Pharmacology Drug Development and Therapeutics
Turku Center for Disease Modeling Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
Functional Foods Forum University of Turku, Turku, Finland
Department of Laboratory Medicine MAS University Hospital, Lund University, Malmö, Sweden
Departments of Cell Biology and Anatomy
Pharmacology Drug Development and Therapeutics
Turku Center for Disease Modeling Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
Functional Foods Forum University of Turku, Turku, Finland
Department of Laboratory Medicine MAS University Hospital, Lund University, Malmö, Sweden
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development of benign prostatic hyperplasia (BPH) and prostate cancer ( Härkönen & Mäkelä 2004 , Prins & Korach 2008 , Ellem & Risbridger 2009 , Hartman et al . 2012 ). In target tissues, estrogens act via estrogen receptor α (ERα) (ESR1) and ERβ (ESR2
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Cancer Drug Discovery Laboratory, Department of Biochemistry, Invasion and Metastasis Laboratory, Prince Henry's Institute, 246 Clayton Road, Melbourne, Victoria 3168, Australia
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Cancer Drug Discovery Laboratory, Department of Biochemistry, Invasion and Metastasis Laboratory, Prince Henry's Institute, 246 Clayton Road, Melbourne, Victoria 3168, Australia
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also an ERα target gene ( Annicotte et al . 2005 ) in MCF-7 cells. To determine whether LRH-1-dependent cell migration occurs independently of oestrogen, we repeated these experiments using the ER-negative MDA-MB-231 cell line and obtained similar
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418 were obtained from Life Technologies. Human insulin and Matrigel were obtained from Sigma Chemical Company. Antibodies against phospho-ERα (S118 and S167) were purchased from Millipore (Billerica, MA, USA). Antibodies against p-Akt and Akt were
Deeley Research Centre, Department of Biochemistry and Microbiology, Department of Biochemistry and Medical Genetics, Department of Pathology and Laboratory Medicine, BC Cancer Agency, 2410 Lee Avenue, 3rd Floor Research, Victoria, British Columbia, Canada V8R 6V5
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Deeley Research Centre, Department of Biochemistry and Microbiology, Department of Biochemistry and Medical Genetics, Department of Pathology and Laboratory Medicine, BC Cancer Agency, 2410 Lee Avenue, 3rd Floor Research, Victoria, British Columbia, Canada V8R 6V5
Deeley Research Centre, Department of Biochemistry and Microbiology, Department of Biochemistry and Medical Genetics, Department of Pathology and Laboratory Medicine, BC Cancer Agency, 2410 Lee Avenue, 3rd Floor Research, Victoria, British Columbia, Canada V8R 6V5
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Introduction Oestrogen receptor alpha (ERα) is a central factor in breast cell biology and growth. As the primary transcription factor that mediates oestrogen signalling, ER is the linchpin of endocrine therapy and a feature that partly defines the
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express estrogen receptor alpha (ERα) and respond to antiestrogen therapies. These carcinomas may also express progesterone receptors (PRs), which are a reliable marker of functional ERs ( Kastner et al . 1990 , Petz & Nardulli 2000 ). In this paper, we
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transcriptional upregulation of cyclin D1 mRNA and protein expression ( Prall et al . 1998 ). In addition, membrane-associated ERα molecules induce rapid activation of c-Src and MAPKs and are capable of transactivation of epidermal growth factor (EGFR) in breast
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Introduction There are large-scale molecular differences between estrogen receptor α (ERα)-positive and ER-negative breast cancers ( Sorlie et al . 2003 ). ER is essential for estrogen-dependent growth, and its level of expression is a crucial
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Department of Experimental Oncology, Molecular Cancer Genetics, Departments of Medical Oncology, Surgery, Pathology, Scientific Direction, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy
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Department of Experimental Oncology, Molecular Cancer Genetics, Departments of Medical Oncology, Surgery, Pathology, Scientific Direction, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy
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Department of Experimental Oncology, Molecular Cancer Genetics, Departments of Medical Oncology, Surgery, Pathology, Scientific Direction, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy
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Department of Experimental Oncology, Molecular Cancer Genetics, Departments of Medical Oncology, Surgery, Pathology, Scientific Direction, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy
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Department of Experimental Oncology, Molecular Cancer Genetics, Departments of Medical Oncology, Surgery, Pathology, Scientific Direction, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy
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This study aimed to define a gene expression profile associated with response to anti-estrogen treatment in estrogen receptor α (ERα)-positive breast cancer from elderly patients and to identify possible candidate genes associated with resistance by detecting those modulated by treatment. Using cDNA microarrays containing 16 702 unique clones, 21 pre-treatment and 11 paired post-treatment samples collected in a neo-adjuvant toremifene trial on elderly patients with operable and locally advanced ERα-positive breast cancer were profiled. Gene expression profiles generated from pre-treatment samples were correlated with treatment-induced tumor shrinkage and compared with those obtained from post-treatment paired samples to define genes differentially modulated following anti-estrogen treatment. Correlation analysis on 21 pre-treatment samples highlighted 53 genes significantly related to treatment response (P<0.001). Genes involved in cell cycle and proliferation were more frequently upregulated in responders compared with non-responders. Class comparison analysis identified 101 genes significantly modulated independently of treatment response; 82 genes were modulated in non-responders, whereas only 8 genes were differently expressed after treatment in responders. Gene expression profiles appear to be more frequently modulated by anti-estrogen treatment in non-responding patients and may harbor interesting genes possibly involved in anti-estrogen resistance, including clusterin, MAPK6, and MMP2. This concept was corroborated by in vitro studies showing that silencing of CLU restored toremifene sensitivity in the ER anti-estrogen-resistant breast cancer cell line T47D. Integration between neo-adjuvant therapy and transcriptional profiling has therefore the potential to identify therapeutic targets to be challenged for overcoming treatment resistance.
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deprivation provides an effective therapeutic second line strategy in advanced postmenopausal estrogen receptor positive (ERα+) breast cancer ( Johnston & Dowsett 2003 ). Moreover, emerging trial data indicate that AIs may be superior to the antiestrogen
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Introduction Drugs that function by inhibiting ERα signaling have been and will continue to be an important part of pharmacotherapy in breast cancer. Foremost among these therapies are selective estrogen receptor modulators (SERMs