G protein-coupled receptors provide survival signals in prostate cancer.
Prostate cancer is the leading cause for noncutaneous cancer-related deaths among men in the United States. The disease is biologically characterized as being either androgen dependent or androgen independent. Whereas androgen-dependent prostate cancer can be successfully treated with androgen ablative therapy, to date no cure exists for androgen-independent disease. Mechanisms involved in the progression of prostate cancer to androgen independence are not known. Here we present evidence that in addition to growth factor receptor tyrosine kinases, G protein- coupled receptors can mediate survival signals in prostate cancer cells. The G protein- coupled receptors exert their effects by activating multiple intracellular signal transduction networks that promote prostate cancer cell survival, including the activation of c-Jun N-terminal kinase, protein kinase B (Akt) and nuclear factor-kB. Prostate-expressed G protein- coupled receptors and their downstream effectors may prove to be effective targets in the treatment of advanced prostate cancer.
Yowell
Charles W
CW
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Daaka
Yehia
Y
D002470:Cell Survival; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins