Pharmaceutical Sciences Faculty Publications

Title

Regulation of Androgen Receptor Activity by Tyrosine Phosphorylation

Document Type

Article

Publication Date

10-1-2006

Journal Title

Cancer Cell

ISSN

1535-6108

Volume

10

Issue

4

First Page

309

Last Page

319

DOI

10.1016/j.ccr.2006.08.021

PubMed ID

17045208

Abstract

The androgen receptor (AR) is essential for the growth of prostate cancer cells. Here, we report that tyrosine phosphorylation of AR is induced by growth factors and elevated in hormone-refractory prostate tumors. Mutation of the major tyrosine phosphorylation site in AR significantly inhibits the growth of prostate cancer cells under androgen-depleted conditions. The Src tyrosine kinase appears to be responsible for phosphorylating AR, and there is a positive correlation of AR tyrosine phosphorylation with Src tyrosine kinase activity in human prostate tumors. Our data collectively suggest that growth factors and their downstream tyrosine kinases, which are elevated during hormone-ablation therapy, can induce tyrosine phosphorylation of AR and such modification may be important for prostate tumor growth under androgen-depleted conditions.

Keywords

Androgens, cell line, tumor, chlorocebus aethiops, dihydrotestosterone, epidermal growth factor, gene expression regulation, neoplastic, immunohistochemistry, indoles, kinetics, phosphorylation, prostatic neoplasms, pyrimidines, receptors, sulfonamides, tyrosine

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