An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial cell apoptosis

Abstract

The prostate gland in adult male rats is highly dependent on androgenic steroids. Castration initiates the regression of this tissue through a process involving the loss of the vast majority of cells by means of apoptosis. We studied this well characterized in vivo model of apoptosis to evaluate how the expression of two particular gene products, bcl-2 and bax, known to be important for the regulation of apoptosis were affected by castration. An RNase protection assay designed to quantify the levels of bax mRNA showed that this transcript was transiently elevated after castration, reaching a peak in expression at 3 days and declining thereafter. In contrast, bcl-2 mRNA expression was continuously elevated over a period of up to 7 days after castration. The distinct changes in the expression of the mRNAs encoding these two genes were confirmed by an in situ hybridization analysis of regressing rat ventral prostate tissues. The elevation in mRNAs were apparently restricted to the secretory epithelial cells of the gland, the cellular compartment of the tissue most affected by castration. Finally, SDS - PAGE/Western blot analysis of bax and bcl-2 protein expression in the regressing rat prostate gland with bax and bcl-2-specific antibodies showed that the changes in the bax and bcl-2 protein levels were similar and consistent to that found for the mRNAs. In summary, the expression of both bax and bcl-2 gene products are uniquely modulated during castration-induced regression of the rat ventral prostate gland. The changes we observed identify a transient but marked increase in the bax/bcl-2 expression ratio of the tissue that peaks on the second and third days after castration, coinciding with the peak periods of prostate cell apoptosis. These data support previous studies done on in vitro systems wherein it was shown that the bax/bcl-2 ratio determines the apoptotic potential of a cell.