BCL-2 in prostate cancer: a minireview.
Prostate cancer progression and the development of androgen-independent prostate cancer have been largely related to a number of genetic abnormality that affect not only the androgen receptor but also crucial molecules involved in the regulation of survival or apoptotic pathways. One of these molecules, the pro-survival protein BCL-2, has been associated with the development of androgen-independent prostate cancer due to its high levels of expression in androgen-independent tumors in advanced stages of the pathology. The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further established a connection between BCL-2 expression and prostate cancer progression. This review focuses on the experimental evidence that associates BCL-2 expression with prostate carcinogenesis and cancer progression, and analyzes the evidence that links the phosphatidylinositol 3-kinase (PI 3-kinase)/nuclear factor kappa B (NF-kappaB) survival pathway with the upregulation of BCL-2. The way in which hormone ablation influences this survival pathway and the potential application of novel therapeutic strategies to overcome this anti-apoptotic mechanism is examined.
Catz
S D
SD
Biochemistry Division, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. scatz@scripps.edu
Johnson
J L
JL
D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000728:Androgens; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases