Reference : Regulation by androgens of EGF receptor family members in prostate cancer cells
Scientific congresses and symposiums : Paper published in a journal
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
Human health sciences : Urology & nephrology
http://hdl.handle.net/2268/39026
Regulation by androgens of EGF receptor family members in prostate cancer cells
English
Pignon, Jean-Christophe [ > > ]
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 > Département des sciences cliniques > Urologie - GIGA-R : Labo de recherche sur les métastases >]
Winkler, Rose mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
2006
Proceedings of the American Association for Cancer Research
Yes
No
International
0569-2261
97th annual meeting of the American Association for Cancer Research
1-5 avril 2006
American Association for Cancer Research
Washington, DC
United States of America
[en] androgen ; ERBB1 ; ERBB2 ; prostate cancer
[en] After an initial positive response to anti-androgen treatment, prostate cancer (PCa) cells usually become hormone-refractory in spite of their persistent expression of the androgen receptor (AR). Overexpression of tyrosine kinase receptors in androgen-deprived PCa cells, such as those of the EGF receptor (EGFR) family, may be responsible for AR activation and growth of androgen-deprived tumours.
Our goal is to understand the control of the expression of the EGFR family members by androgens in PCa.
Hormone response was compared in hormone-sensitive LNCaP and hormone-insensitive DU145 PCa cell lines. These cells do not express ErbB4. EGFR, erbB2 and erbB3 protein half-life is much longer in DU145 than in LNCaP cells grown in complete medium. Dihydrotestosterone (DHT) modulates EGFR and erbB2 transcript and protein levels only in LNCaP cells. ErbB3 is not an androgen-responsive gene. EGFR mRNA and protein levels are increased while erbB2 mRNA and protein levels are decreased after DHT treatment of cells cultured in steroid-deprived medium. ErbB2 mRNA and protein levels are increased in LNCaP cells following DHT withdrawal. In order to understand the mechanisms by which androgens control the expression of EGFR and ERBB2 genes, half lifes of the corresponding mRNAs and proteins were compared in cells grown in presence or absence of DHT. The effect of DHT on EGFR gene expression is complex. Indeed, DHT stabilizes the protein. Moreover, a superinduction of EGFR mRNA was observed in cells treated with cycloheximide (CHX) before addition of the hormone, suggesting an effect on transcript stability. In contrast, erbB2 mRNA and protein stability was not affected by DHT. CHX treatment for 2h before addition of DHT suppresses the androgen-induced down-regulation of erbB2 mRNA levels.
In summary, androgen-mediated regulation of EGFR and ERBB2 genes expression is complex. DHT influences EGFR gene transcription, mRNA and protein stability. DHT does not affect erbB2 mRNA and protein stability but acts indirectly on transcription. Current experiments are undertaken to verify these observations by Chromatin-IP experiments on both genes promoters.
http://hdl.handle.net/2268/39026

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
AACR androgens 2006.pdfPublisher postprint105.25 kBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.