DECREASED LEVELS OF P26-BCL-2, BUT NOT P-30 PHOSPHORYLATED BCL-2, PRECEDE TGF-BETA(1)-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 a denoma cells, TGF beta induces a growth arrest. In some adenoma cell l ines, this is accompanied by apoptosis and in others it is not. In thi s 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 in duce apoptosis in RG/C2 cells even if hydrocortisone and insulin are r emoved from the culture medium. In BH/C1 cells, TGF beta induces apopt osis in the presence of insulin and hydrocortisone. Apoptosis induced by TGF beta is preceded by a reduction in p26-Bcl-2 protein levels, Th ere 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 d id not show decreased Bcl-2 levels in response to TGF beta-induced gro wth inhibition. Therefore, TGF beta regulates Bcl-2 expression in colo nic adenoma cells which undergo apoptosis in response to TGF beta, but not in those which are growth inhibited, but resistant to TGF beta-in duced apoptosis, TGF beta may play an important role in the colonic ep ithelium, not only in the inhibition of cell proliferation, but also i n the regulation of apoptosis.