JLE

Bulletin du Cancer

MENU

Androgen-independent prostate carcinoma and androgen-receptor: recent progress in molecular genetics Volume 86, issue 7-8, Numéro double 7 - 8, Juillet - Août 1999

Figures

See all figures

Authors
Inserm U. 439, Pathologie moléculaire des récepteurs nucléaires, 70, rue de Navacelles, 34090 Montpellier.

Prostate cancer is an androgen-dependant tumor which presents an androgen-independant regrowth after clinical regression in response to antiandrogen treatment. Four hypotheses have been developped to understand how androgen signal transduction pathway mediate androgen-independent tumor progression: over expression of the wild-type androgen-receptor gene, androgen-receptor gene mutation, excessive recruitement of transcriptional co-activator ARA-70 and a cross-talk between the androgen-receptor and the growth factor receptor pathways. In this work, C. Sawyers’s group elegantly demonstrates, in LAPC-4 androgen-independent prostate cancer sublines, that forced hyperexpression of HER-2/Neu receptor thyrosine kinase allowed androgen-independent growth, that HER-2/Neu activated the androgen-receptor pathway in the absence of androgens and synergized with low levels of androgen to superactivate the pathway. These important data could have therapeutic implications for the management of androgen-independant prostate cancer.