Overexpression of bcl-2 Protects Prostate Cancer Cells from Apoptosis in Vitro and Confers Resistance to Androgen Depletion in Vivo

摘要: Normal (nonneoplastic) human prostatic secretory epithelial cells do not express the bcl-2 protein. However, a recent immunohistochemical survey of neoplastic prostate tissues showed that fraction primary untreated adenocarcinoma expressed this apoptosis-suppressing oncoprotein at significant levels (Colombel et al., Am. J. Pathol., 143: 390-400, 1993). Additionally, number hormone-refractory adenocarcinomas obtained from hormonally-treated patients (subsequent to surgical or drug castration therapy) were examined and found be uniform in their elevated expression oncoprotein. The results preliminary imply distinguishes subgroup cancers protein might factor enabling cancer survive an androgen-deprived environment. current study was undertaken determine degree which overexpression can protect apoptotic stimuli vitro vivo. Human (LNCaP) transfected with neomycin-selectable eucaryotic vector containing cDNA encoding bcl-2. Transfected clonal variants (LNCaP/bcl-2) unaltered regard basal growth rate 10% serum-containing medium, differentiated cell gene products prostate-specific antigen androgen receptor bcl-2-transfected clones altered, however, charcoal-stripped serum lacking dihydrotestosterone. contrast parental control-transfected lines, LNCaP/bcl-2 highly resistant variety including starvation 10 nM phorbol ester (phorbol 12-myristate 13-acetate) supplementation medium. Lastly, by these altered tumorigenic potential nude mouse assay. s.c. injections 10(6) into male mice resulted earlier larger tumor formation compared equivalent injection LNCaP cells. When variant lines injected castrated mice, only LNCaP/bcl-2-transformed gave rise tumors. Moreover, tumors grown intact refractory growth-inhibiting effects demonstrated Data demonstrate suggest such protection correlates ability form