[Androgen-independent prostate carcinoma and androgen-receptor: recent progress in molecular genetics].
Prostate cancer is an androgen-dependent tumor which presents an androgen-independent regrowth after clinical regression in response to antiandrogen treatment. Four hypotheses have been developed 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 recruitment 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 tyrosine 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-independent prostate cancer.
Sultan
C
C
Inserm U. 439, Pathologie moléculaire des récepteurs nucléaires, 70, rue de Navacelles, 34090 Montpellier.
Terouanne
B
B
Tahiri
B
B
Lumbroso
S
S
Avances
C
C
Orio
F
F
D018450:Disease Progression; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
D017430:Prostate-Specific Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen