Decreased levels of p26-Bcl-2, but not p30 phosphorylated Bcl-2, precede TGFbeta1-induced apoptosis in colorectal adenoma cells

Bcl-2 expression is confined to the base of the colonic crypt, whereastransforming growth factor beta (TGFbeta) is expressed in the upper crypt,as are the apoptotic death promoters, Bak and Bax. In colonic adenomacells, TGFbeta induces a growth arrest. In some adenoma cell lines, this isaccompanied by apoptosis and in others it is not. In this study, we usedtwo human colonic adenoma cell lines: RG/C2, in which TGFbeta induces a G1arrest without apoptosis, and BH/C1, in which TGFbeta induces both a G1arrest and apoptosis. TGFbeta does not induce apoptosis in RG/C2 cells evenif hydrocortisone and insulin are removed from the culture medium. In BH/C1cells, TGFbeta induces apoptosis in the presence of insulin andhydrocortisone. Apoptosis induced by TGFbeta is preceded by a reduction inp26-Bcl-2 protein levels. There was no change in the levels of the p30phosphorylated form of Bcl-2 or in levels of the proapoptotic proteins Baxor Bak. RG/C2 cells did not show decreased Bcl-2 levels in response toTGFbeta- induced growth inhibition. Therefore, TGFbeta regulates Bcl-2expression in colonic adenoma cells which undergo apoptosis in response toTGFbeta, but not in those which are growth inhibited, but resistant toTGFbeta-induced apoptosis. TGFbeta may play an important role in thecolonic epithelium, not only in the inhibition of cell proliferation, butalso in the regulation of apoptosis.