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.
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September 2002
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Research Article|
September 15 2002
Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells
Michèle MANIN;
Michèle MANIN
∗UMR CNRS 6547, Equipe Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Les Cézeaux, 63177, Aubière Cedex, France,
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Silvère BARON;
Silvère BARON
∗UMR CNRS 6547, Equipe Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Les Cézeaux, 63177, Aubière Cedex, France,
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Karine GOOSSENS;
Karine GOOSSENS
†Laboratory for Experimental Medicine and Endocrinology, Onderwijs en Narvorsing, Gasthuisberg, Catholic University of Leuven, B-3000 Leuven, Belgium
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Claude BEAUDOIN;
Claude BEAUDOIN
∗UMR CNRS 6547, Equipe Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Les Cézeaux, 63177, Aubière Cedex, France,
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Claude JEAN;
Claude JEAN
∗UMR CNRS 6547, Equipe Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Les Cézeaux, 63177, Aubière Cedex, France,
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Georges VEYSSIERE;
Georges VEYSSIERE
∗UMR CNRS 6547, Equipe Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Les Cézeaux, 63177, Aubière Cedex, France,
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Guido VERHOEVEN;
Guido VERHOEVEN
†Laboratory for Experimental Medicine and Endocrinology, Onderwijs en Narvorsing, Gasthuisberg, Catholic University of Leuven, B-3000 Leuven, Belgium
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Laurent MOREL
Laurent MOREL
1
∗UMR CNRS 6547, Equipe Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal, Les Cézeaux, 63177, Aubière Cedex, France,
1To whom correspondence should be addressed (e-mail laurent.morel@univ-bpclermont.fr).
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Publisher: Portland Press Ltd
Received:
April 11 2002
Accepted:
April 24 2002
Accepted Manuscript online:
April 24 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 366 (3): 729–736.
Article history
Received:
April 11 2002
Accepted:
April 24 2002
Accepted Manuscript online:
April 24 2002
Citation
Michèle MANIN, Silvère BARON, Karine GOOSSENS, Claude BEAUDOIN, Claude JEAN, Georges VEYSSIERE, Guido VERHOEVEN, Laurent MOREL; Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells. Biochem J 15 September 2002; 366 (3): 729–736. doi: https://doi.org/10.1042/bj20020585
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