Decreased levels of p26-Bcl-2, but not p30 phosphorylated Bcl-2, precede TGFβ1-induced apoptosis in colorectal adenoma cells

Bcl-2 expression is confined to the base of the colonic crypt, whereas transforming growth factor beta (TGF beta) is expressed in the upper crypt, as are the apoptotic death promoters, Bah and Bar. In colonic adenoma cells, TGF beta induces a growth arrest. In some adenoma cell lines, this is accompanied by apoptosis and in others it is not. In this study, we used two human colonic adenoma cell lines: RG/C2, in which TGF beta induces a G(1) arrest without apoptosis, and BH/C1, in which TGF beta induces both a GI arrest and apoptosis, TGF beta does not induce apoptosis in RG/C2 cells even if hydrocortisone and insulin are removed from the culture medium. In BH/C1 cells, TGF beta induces apoptosis in the presence of insulin and hydrocortisone. Apoptosis induced by TGF beta is preceded by a reduction in p26-Bcl-2 protein levels, There was no change in the levels of the p30 phosphorylated form of Bcl-2 or in levels of the pro-apoptotic proteins Bar or Bah, RG/C2 cells did not show decreased Bcl-2 levels in response to TGF beta-induced growth inhibition. Therefore, TGF beta regulates Bcl-2 expression in colonic adenoma cells which undergo apoptosis in response to TGF beta, but not in those which are growth inhibited, but resistant to TGF beta-induced apoptosis, TGF beta may play an important role in the colonic epithelium, not only in the inhibition of cell proliferation, but also in the regulation of apoptosis.