[HTML][HTML] Steroid‐induced androgen receptor–oestradiol receptor β–Src complex triggers prostate cancer cell proliferation

A Migliaccio, G Castoria, M Di Domenico… - The EMBO …, 2000 - embopress.org
A Migliaccio, G Castoria, M Di Domenico, A de Falco, A Bilancio, M Lombardi, MV Barone…
The EMBO journal, 2000embopress.org
Abstract Treatment of human prostate carcinoma‐derived LNCaP cells with androgen or
oestradiol triggers simultaneous association of androgen receptor and oestradiol receptor β
with Src, activates the Src/Raf‐1/Erk‐2 pathway and stimulates cell proliferation.
Surprisingly, either androgen or oestradiol action on each of these steps is inhibited by both
anti‐androgens and anti‐oestrogens. Similar findings for oestradiol receptor α were
observed in MCF‐7 or T47D cells stimulated by either oestradiol or androgens …
Abstract
Treatment of human prostate carcinoma‐derived LNCaP cells with androgen or oestradiol triggers simultaneous association of androgen receptor and oestradiol receptor β with Src, activates the Src/Raf‐1/Erk‐2 pathway and stimulates cell proliferation. Surprisingly, either androgen or oestradiol action on each of these steps is inhibited by both anti‐androgens and anti‐oestrogens. Similar findings for oestradiol receptor α were observed in MCF‐7 or T47D cells stimulated by either oestradiol or androgens. Microinjection of LNCaP, MCF‐7 and T47D cells with SrcK− abolishes steroid‐stimulated S‐phase entry. Data from transfected Cos cells confirm and extend the findings from these cells. Hormone‐stimulated Src interaction with the androgen receptor and oestradiol receptor α or β is detected using glutathione S‐transferase fusion constructs. Src SH2 interacts with phosphotyrosine 537 of oestradiol receptor α and the Src SH3 domain with a proline‐rich stretch of the androgen receptor. The role of this phosphotyrosine is stressed by its requirement for association of oestradiol receptor α with Src and consequent activation of Src in intact Cos cells.
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