Paradoxical inhibition of c-myc-induced carcinogenesis by Bcl-2 in transgenic mice

Here, we investigated changes in apoptosis during tumor progression by anal yzing the effect of coexpressing various antiapoptotic genes on the multist age process of c-myc-induced hepatocarcinogenesis in transgenic mice. Where as continuous c-myc gene overexpression in the liver led to cellular hepato carcinoma, the coexpression of the bcl-2 gene inhibited the emergence of li ver tumors, by inhibiting a pretumoral phase characterized by increased pro liferation and apoptosis. This antioncogenic effect was specific to Bcl-2 a nd was not shared by other antiapoptotic genes such as bcl-x(L) and a domin ant negative form of p53. Thus, we have shown that Bcl-2 can have a tumor s uppressor effect in vivo on c-myc-induced hepatocarcinogenesis during the e mergence of neoplastic foci.