Effect of Bcl‐2 overexpression in human prostate cancer cells in vitro and in vivo

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Abstract
Background : Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti‐apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl‐2 and its family members are best characterized. Methods : To investigate the effect of bcl‐2‐mediated anti‐apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl‐2 (LNCaP/bcl‐2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl‐2 was compared with the parental cell line in vitro and in vivo. Results : LNCaP/bcl‐2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum‐free or androgen‐free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum‐free or androgen‐free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl‐2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl‐2‐derived tumors showed resistance, as was previously reported. Conclusions : These data confirm the notion that anti‐apoptotic function of bcl‐2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.