Signal transduction in prostate cancer progression.
Prostate cancer is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths in the United States. When prostate cancer initially presents in the clinic, the tumour is dependent on androgen for growth and, therefore, responsive to the surgical or pharmacological ablation of circulating androgens. However, there is a high rate of treatment failure because the disease often recurs as androgen-independent metastases. Surprisingly, this late-stage androgen-independent prostate cancer almost always retains expression of the AR (androgen receptor), despite the near absence of circulating androgens. Although late-stage prostate cancer is androgen-independent, the AR still seems to play a role in cancer cell growth at this stage of disease. Therefore a key to understanding hormone-independent prostate cancer is to determine the mechanism(s) by which the AR can function even in the absence of physiological levels of circulating androgen. This review will focus on the role of growth factor signalling in prostate cancer progression to androgen independence and thus outline potential molecular areas of intervention to treat prostate cancer progression.
Gioeli
Daniel
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Department of Microbiology, University of Virginia Health System, PO Box 800734, Charlottesville, VA 22908, U.S.A. DGioeli@virginia.edu
D018450:Disease Progression; D011905:Genes, ras; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000503:physiopathology; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000502:physiology; D015398:Signal Transduction; D018631:ras Proteins / Q000502:physiology
D006133:Growth Substances; D011944:Receptors, Androgen; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins