Regulation of androgen receptor activity by tyrosine phosphorylation.

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TitleRegulation of androgen receptor activity by tyrosine phosphorylation.
Publication TypeJournal Article
Year of Publication2006
AuthorsGuo, Z, Dai, B, Jiang, T, Xu, K, Xie, Y, Kim, O, Nesheiwat, I, Kong, X, Melamed, J, Handratta, VD, Njar, VCO, Brodie, AMH, Yu, L-R, Veenstra, TD, Chen, H, Qiu, Y
JournalCancer Cell
Volume10
Issue4
Pagination309-19
Date Published2006 Oct
ISSN1535-6108
KeywordsAndrogens, Animals, Cell Line, Tumor, Cercopithecus aethiops, COS Cells, Dihydrotestosterone, Epidermal Growth Factor, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Indoles, Interleukin-6, Kinetics, Male, Mice, Mice, SCID, Neuregulin-1, Phosphorylation, Prostatic Neoplasms, Pyrimidines, Receptors, Androgen, src-Family Kinases, Sulfonamides, Tyrosine, Xenograft Model Antitumor Assays
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.

DOI10.1016/j.ccr.2006.08.021
Alternate JournalCancer Cell
PubMed ID17045208
Grant ListCA106504 / CA / NCI NIH HHS / United States
CA85380 / CA / NCI NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States
T32ES07263 / ES / NIEHS NIH HHS / United States
U01-CA86772 / CA / NCI NIH HHS / United States