Reference : Androgen receptor controls EGFR and ERBB2 gene expression at different levels in pros...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Endocrinology, metabolism & nutrition
http://hdl.handle.net/2268/26361
Androgen receptor controls EGFR and ERBB2 gene expression at different levels in prostate cancer cell lines.
English
Pignon, Jean-Christophe mailto [Université de Liège - ULg > > > Doct. sc. bioméd. & pharma. (Bologne)]
Koopmansch, Benjamin mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > GIGA-R : Oncologie moléculaire >]
Nolens, Grégory mailto [Université de Liège - ULg > > > GIGA - Membres]
Delacroix, Laurence mailto [Université de Liège - ULg > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Waltregny, David mailto [Université de Liège - ULg > > Urologie >]
Winkler, Rose mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
1-Apr-2009
Cancer Research
American Association for Cancer Research, Inc. (AACR)
69
7
2941-2949
Yes (verified by ORBi)
International
0008-5472
1538-7445
Baltimore
MD
[en] Androgen receptor ; ERBB ; prostate cancer
[en] EGFR or ERBB2 contributes to prostate cancer (PCa) progression by activating the androgen receptor (AR) in hormone-poor conditions. Here, we investigated the mechanisms by which androgens regulate EGFR and ERBB2 expression in PCa cells. In steroid-depleted medium (SDM), EGFR protein was less abundant in androgen-sensitive LNCaP than in androgen ablation-resistant 22Rv1 cells, whereas transcript levels were similar. Dihydrotestosterone (DHT) treatment increased both EGFR mRNA and protein levels and stimulated RNA polymerase II recruitment to the EGFR gene promoter, whereas it decreased ERBB2 transcript and protein levels in LNCaP cells. DHT altered neither EGFR or ERBB2 levels nor the abundance of prostate-specific antigen (PSA), TMEPA1, or TMPRSS2 mRNAs in 22Rv1 cells, which express the full-length and a shorter AR isoform deleted from the COOH-terminal domain (ARDeltaCTD). The contribution of both AR isoforms to the expression of these genes was assessed by small interfering RNAs targeting only the full-length or both AR isoforms. Silencing of both isoforms strongly reduced PSA, TMEPA1, and TMPRSS2 transcript levels. Inhibition of both AR isoforms did not affect EGFR and ERBB2 transcript levels but decreased EGFR and increased ERBB2 protein levels. Proliferation of 22Rv1 cells in SDM was inhibited in the absence of AR and ARDeltaCTD. A further decrease was obtained with PKI166, an EGFR/ERBB2 kinase inhibitor. Overall, we showed that ARDeltaCTD is responsible for constitutive EGFR expression and ERBB2 repression in 22Rv1 cells and that ARDeltaCTD and tyrosine kinase receptors are necessary for sustained 22Rv1 cell growth.
Giga-Cancer
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Centre Anti-Cancéreux de l'université de Liège
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/26361
also: http://hdl.handle.net/2268/36213

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