Androgen receptor activation by G(s) signaling in prostate cancer cells.
The androgen receptor (AR) is activated in prostate cancer patients undergoing androgen ablative therapy and mediates growth of androgen-insensitive prostate cancer cells, suggesting it is activated by nonandrogenic factors. We demonstrate that activated alpha subunit of heterotrimeric guanine nucleotide-binding G(s) protein activates the AR in prostate cancer cells and also synergizes with low concentration of androgen to more fully activate the AR. The G alpha(s) activates protein kinase A, which is required for the nuclear partition and activation of AR. These data suggest a role for G alpha(s) and PKA in the transactivation of AR in prostate cancer cells under the environment of reduced androgen levels.
Kasbohm
Elizabeth A
EA
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Guo
Rishu
R
Yowell
Charles W
CW
Bagchi
Gargi
G
Kelly
Patrick
P
Arora
Puneeta
P
Casey
Patrick J
PJ
Daaka
Yehia
Y
D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D013196:Dihydrotestosterone / Q000494:pharmacology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000502:physiology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D011944:Receptors, Androgen / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D018343:Receptors, Adrenergic, beta-2; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs; D007545:Isoproterenol