title: Regulation of androgen receptor activity by tyrosine phosphorylation.
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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
authors.forename: Bojie
authors.initials: B
authors.lastname: Dai
authors.forename: Tianyun
authors.initials: T
authors.lastname: Jiang
authors.forename: Kexin
authors.initials: K
authors.lastname: Xu
authors.forename: Yingqiu
authors.initials: Y
authors.lastname: Xie
authors.forename: Oekyung
authors.initials: O
authors.lastname: Kim
authors.forename: Issa
authors.initials: I
authors.lastname: Nesheiwat
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Kong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.forename: Venkatesh D
authors.initials: VD
authors.lastname: Handratta
authors.forename: Vincent C O
authors.initials: VC
authors.lastname: Njar
authors.forename: Angela M H
authors.initials: AM
authors.lastname: Brodie
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Yu
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Hegang
authors.initials: H
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D013196:Dihydrotestosterone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D016513:Mice, SCID; D020890:Neuregulin-1 / Q000494:pharmacology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014443:Tyrosine / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: C412373:AG 1879; D000728:Androgens; D007211:Indoles; D015850:Interleukin-6; D020890:Neuregulin-1; D011743:Pyrimidines; D011944:Receptors, Androgen; C416927:SU 6656; D013449:Sulfonamides; D013196:Dihydrotestosterone; C087230:heregulin beta1; D014443:Tyrosine; D004815:Epidermal Growth Factor; D019061:src-Family Kinases