[HTML][HTML] Steroid‐induced androgen receptor–oestradiol receptor β–Src complex triggers prostate cancer cell proliferation
The EMBO journal, 2000•embopress.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 …
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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