HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway

HER-2/neu has been implicated in the activation of androgen receptor (AR) a nd in inducing hormone-independent prostate cancer growth. Here we report t hat HER-2/neu activates Akt (protein kinase B) to promote prostate cancer c ell survival and growth in the absence of androgen. Blocking of the Akt pat hway by a dominant-negative Akt or an inhibitor LY294002 abrogates the HER- 2/neu-induced AR signaling and cell survival/growth effects in the absence or presence of androgen. Akt specifically binds to AR and phosphorylates se rines 213 and 791 of AR. Thus, Akt is a novel activator of AR required for HER-2/neu signaling to androgen-independent survival and growth of prostate cancer cells.