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| The EMBO Journal
(2000) 19, 5406–5417, doi:10.1093/emboj/19.20.5406 |
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Steroid-induced androgen receptor–oestradiol receptor  –Src complex triggers prostate cancer cell proliferation |
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| Antimo Migliaccio1, Gabriella Castoria1, Marina Di Domenico1, Antonietta de Falco1, Antonio Bilancio1, Maria Lombardi1, Maria Vittoria Barone2, Donatella Ametrano1, Maria Stella Zannini3, Ciro Abbondanza1 and Ferdinando Auricchio1 |
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3 Istituto di Patologia Generale e Oncologia, Facoltà di Medicina e Chirurgia, II Università di Napoli, Largo S. Aniello a Caponapoli 2, 80138 Napoli, Italy 1 Dipartimento di Biologia e Patologia Cellulare e Molecolare 'L. Califano', Via Pansini 5, 80131 Napoli Italy 2 Stazione Zoologica 'Anton Dohrn', vl Acquario 1, 80144 Napoli, Italy To whom correspondence should be addressed Ferdinando Auricchio, ferdinando.auricchio@unina2.it Received 2 June 2000; Revised 9 August 2000; Accepted 25 August 2000. |
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| Abstract |
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Treatment of human prostate carcinoma-derived LNCaP cells with androgen or oestradiol triggers simultaneous association of androgen receptor and oestradiol receptor 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  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 or is detected using glutathione S-transferase fusion constructs. Src SH2 interacts with phosphotyrosine 537 of oestradiol receptor 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 with Src and consequent activation of Src in intact Cos cells. |
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| Keywords: androgen receptor, cross-talk, oestradiol receptor, Src association |
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