Regulation of androgen receptor activity by tyrosine phosphorylation.
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.
Guo
Zhiyong
Z
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Dai
Bojie
B
Jiang
Tianyun
T
Xu
Kexin
K
Xie
Yingqiu
Y
Kim
Oekyung
O
Nesheiwat
Issa
I
Kong
Xiangtian
X
Melamed
Jonathan
J
Handratta
Venkatesh D
VD
Njar
Vincent C O
VC
Brodie
Angela M H
AM
Yu
Li-Rong
LR
Veenstra
Timothy D
TD
Chen
Hegang
H
Qiu
Yun
Y
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
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