Bcl-2 protein expression correlates with cell survival and androgen independence in rat prostatic lobes.

Abstract

Castration of young and old male Brown Norway rats induces apoptosis in the ventral, but not in the dorsal and lateral, lobes of the prostate gland, and apoptosis in old rats is diminished by 50% compared with that in young rats. In this study we examined the lobe-specific and age-dependent expression of Bcl-2 and Bax proteins. Bcl-2 levels in the ventral lobe were 5-fold lower compared with expression in the dorsal and lateral lobes. Bax expression in the ventral lobe was 2- and 20-fold higher than that in the lateral and dorsal lobes, respectively. In all three lobes, Bcl-2 was detected in epithelial cells, but not in stromal cells, whereas Bax protein was localized in both cell types. After castration, Bcl-2 expression in the ventral lobe decreased significantly from the control level after 2-3 d, but increased significantly by 7-10 d. By contrast, Bax expression increased significantly by d 1, gradually decreased by 2-4 d, and was nearly undetectable by 7-10 d postcastration. In the dorsal and lateral lobes, neither Bcl-2 nor Bax expression was significantly altered after castration. In the ventral lobe of old rats after castration, Bcl-2 followed a pattern of expression similar to that observed in young rats. However, Bax levels were 50% lower in old rats compared with those in young rats on d 1 after castration. Therefore, cell death follows the down-regulation of Bcl-2 expression in the ventral lobe of young and old rats. Moreover, the higher relative levels of Bcl-2 expression in the dorsal and lateral lobes of intact animals and in the ventral lobe by 7-10 d after castration serve to protect cells from apoptosis.