BCL-2 Expression in Prostate Cancer

Adenocarcinoma of the prostate is the most common malignancy in men and accounts for approximately 40,000 deaths per year in the United States alone. Most of these tumors are initially androgen-dependent and respond to androgen - ablation therapy but invariably progress to an androgen independent state. In the normal prostate gland, androgen depravation leads to massive cell death, occurring through a process that has the morphological characteristics of apoptosis or programmed cell death.

Among the most important regulators of apoptosis and programmed cell death are Bcl-2 and its related proteins. Since the initial discovery of Bcl-2, several homologous proteins have been identified, revealing the presence of a multigene family. Some of   these Bcl-2 family proteins function as blockers of cell death (Bcl-X, Mcl-1), whereas others promote apoptosis (Bax). Interestingly, in most cases, these Bcl-2 family proteins can physically interact with each other through a network of homo and heterodimers, the relative proportions of which ultimately control the sensitivity or resistance of cells to apoptotic stimuli. Using a panel of specific antibodies, researchers have previously determined the patterns of bcl-2, bax, bcl-X, and mcl-1 expression in the prostate gland by immunohistochemical methods. Thus all four of these members of the bcl-2 gene family are expressed in prostate, implying a role for these proteins in controlling cell death under normal circumstances in this gland.

Using immunohistochemical methods scientist have characterized the expression of bcl-2 family genes in human prostate cancers and have correlated these results with Gleason grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate.

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