Alternative use of genes of the closely-related pp32 family is a common occ
urrence in human prostate cancer, pp32r1 and pp32r2, the oncogenic members
of the pp32 family, are expressed in prostatic adenocarcinoma, while adjace
nt benign prostate continues to express pp32, This study focuses upon the r
ole of pp32 in tumor suppression, We demonstrate that antisense inhibition
of pp32 in NIH3T3 cells leads to a variety of phenotypic changes associated
with transformation including reduced serum dependence and loss of contact
inhibition. NIH3T3 cells with antisense-inhibited pp32 are not tumorigenic
, but are markedly more susceptible to oncogenic stimuli such as vas, In co
ntrast, constitutive expression of pp32 abolishes ras mediated transformati
on in vitro and tumorigenesis in vivo. These data demonstrate, from the fun
ctional aspect, that pp32 acts as a tumor suppressor. Furthermore, inactiva
tion of pp32 function through alternative gene use may be a critical event
in tumor evolution and progression.