1. Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells
- Author
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Michèle Manin, Georges Veyssiere, Claude Beaudoin, Laurent Morel, Karine Goossens, Silvère Baron, Claude Jean, and Guido Verhoeven
- Subjects
Male ,Time Factors ,MAP Kinase Signaling System ,Cellular differentiation ,Protein Serine-Threonine Kinases ,Biology ,Transfection ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Cell Line ,Mice ,Phosphatidylinositol 3-Kinases ,Prostate cancer ,Proto-Oncogene Proteins ,LNCaP ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,Phosphorylation ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Regulation of gene expression ,Dose-Response Relationship, Drug ,Prostatic Neoplasms ,Cell Differentiation ,Epithelial Cells ,Cell Biology ,Blotting, Northern ,medicine.disease ,Androgen receptor ,Receptors, Androgen ,Cancer research ,RNA ,Signal transduction ,Proto-Oncogene Proteins c-akt ,Cell Division ,Protein Binding ,Signal Transduction ,Research Article - Abstract
The androgen receptor (AR) is a ligand-responsive transcription factor known to play a central role in the pathogenesis of prostate cancer. However, the regulation of AR gene expression in the normal and pathological prostate remains poorly understood. This study focuses on the effect of the phosphoinositide 3-kinase (PI 3-kinase)/Akt axis on AR expression in vas deferens epithelial cells (VDEC), a suitable model to study androgen regulation of gene expression, and LNCaP cells (derived from a metastasis at the left supraclavicular lymph node from a 50-year-old patient with a confirmed diagnosis of metastatic prostate carcinoma). Taken together, our data show for the first time that the PI 3-kinase/Akt pathway is required for basal and dihydrotestosterone-induced AR protein expression in both VDEC and LNCaP. Inhibition of the PI 3-kinase/Akt pathway reduced AR expression and the decline in AR protein level correlated with a decrease in AR mRNA in VDEC but not in LNCaP. Since PI 3-kinase/Akt axis is active in prostate cancer, cross-talk between PI 3-kinase/Akt and AR signalling pathways may have implications for endocrine therapy.
- Published
- 2002
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