Cancer Research Infection and Cancer: Biology, Therapeutics, and Prevention AACR Conference on Molecular Diagnostics - 2008
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[Cancer Research 60, 6841-6845, December 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

HER-2/neu Promotes Androgen-independent Survival and Growth of Prostate Cancer Cells through the Akt Pathway1

Yong Wen2, Mickey C-T. Hu2, Keishi Makino, Bill Spohn, Geoffrey Bartholomeusz, Duen-Hwa Yan and Mien-Chie Hung3

Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

HER-2/neu has been implicated in the activation of androgen receptor (AR) and in inducing hormone-independent prostate cancer growth. Here we report that HER-2/neu activates Akt (protein kinase B) to promote prostate cancer cell survival and growth in the absence of androgen. Blocking of the Akt pathway 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 serines 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.




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