A. Velcich et Lh. Augenlicht, REGULATED EXPRESSION OF AN INTESTINAL MUCIN GENE IN HT29 COLONIC-CARCINOMA CELLS, The Journal of biological chemistry, 268(19), 1993, pp. 13956-13961
We have investigated the regulation of the intestinal mucin gene MUC2
in HT29 cells. Surprisingly, sodium butyrate, an effective inducer of
aspects of colonic cell differentiation in HT29 cells, fails to induce
MUC2 during short-term exposure, despite the fact that it has been us
ed to select stably differentiated clones of HT29 that resemble goblet
cells and produce mucin. However, 12-O-tetradecanoylphorbol-13-acetat
e and forskolin, which trigger the protein kinase C- and A-dependent s
ignal transduction pathways, respectively, are potent inducers of MUC2
gene expression. 12-O-Tetradecanoylphorbol-13-acetate and forskolin o
perate through distinct mechanisms, with the former requiring de novo
protein synthesis and the latter not. Experiments using specific prote
in kinase inhibitors suggest that both inducers operate by triggering
their respective signal transduction pathways. Nuclear run-off analyse
s suggest that post-transcriptional (rather than transcriptional) mech
anisms are important in the accumulation of MUC2 mRNA. Finally, we sho
w that in several cell lines from human mucinous tumors, characterized
by elevated levels of mucin production, MUC2 expression is very high
and constitutive compared to forskolin-treated HT29 cells. Thus, the d
ifferent regulation of MUC2 in HT29 cells and in mucinous tumor cell l
ines may reflect molecular pathways that characterize colon carcinomas
of different histology and pathology.