Carcinogenesis, Vol 19, 1691-1695, Copyright © 1998 by Oxford University Press
A Hague, TS Bracey, DJ Hicks, JC Reed and C Paraskeva
Bcl-2 expression is confined to the base of the colonic crypt, whereas
transforming growth factor beta (TGFbeta) is expressed in the upper crypt,
as are the apoptotic death promoters, Bak and Bax. In colonic adenoma
cells, TGFbeta 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 TGFbeta induces a G1
arrest without apoptosis, and BH/C1, in which TGFbeta induces both a G1
arrest and apoptosis. TGFbeta does not induce apoptosis in RG/C2 cells even
if hydrocortisone and insulin are removed from the culture medium. In BH/C1
cells, TGFbeta induces apoptosis in the presence of insulin and
hydrocortisone. Apoptosis induced by TGFbeta 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 proapoptotic proteins Bax
or Bak. RG/C2 cells did not show decreased Bcl-2 levels in response to
TGFbeta- induced growth inhibition. Therefore, TGFbeta regulates Bcl-2
expression in colonic adenoma cells which undergo apoptosis in response to
TGFbeta, but not in those which are growth inhibited, but resistant to
TGFbeta-induced apoptosis. TGFbeta may play an important role in the
colonic epithelium, not only in the inhibition of cell proliferation, but
also in the regulation of apoptosis.
ARTICLES
Decreased levels of p26-Bcl-2, but not p30 phosphorylated Bcl-2, precede TGFbeta1-induced apoptosis in colorectal adenoma cells
Department of Pathology and Microbiology, University of Bristol, School of Medical Sciences, University Walk, UK. a.hague@bris.ac.uk
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