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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Androgens / pharmacology
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Animals
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COS Cells
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Cell Line, Tumor
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Chlorocebus aethiops
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Dihydrotestosterone / pharmacology
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Epidermal Growth Factor / pharmacology
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Gene Expression Regulation, Neoplastic / genetics*
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Humans
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Immunohistochemistry
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Indoles / pharmacology
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Interleukin-6 / pharmacology
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Kinetics
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Male
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Mice
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Mice, SCID
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Neuregulin-1 / pharmacology
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Phosphorylation
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Pyrimidines / pharmacology
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Receptors, Androgen / genetics*
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Receptors, Androgen / metabolism*
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Sulfonamides / pharmacology
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Tyrosine / physiology*
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Xenograft Model Antitumor Assays
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / physiology
Substances
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AG 1879
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Androgens
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Indoles
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Interleukin-6
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Neuregulin-1
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Pyrimidines
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Receptors, Androgen
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SU 6656
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Sulfonamides
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Dihydrotestosterone
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heregulin beta1
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Tyrosine
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Epidermal Growth Factor
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src-Family Kinases