Regulated expression of an intestinal mucin gene in HT29 colonic carcinoma cells

Anna Velcich, Leonard H. Augenlicht

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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 used to select stably differentiated clones of HT29 that resemble goblet cells and produce mucin. However, 12-O-tetradecanoylphorbol-13-acetate and forskolin, which trigger the protein kinase C- and A-dependent signal transduction pathways, respectively, are potent inducers of MUC2 gene expression. 12-O-Tetradecanoylphorbol-13-acetate and forskolin operate through distinct mechanisms, with the former requiring de novo protein synthesis and the latter not. Experiments using specific protein kinase inhibitors suggest that both inducers operate by triggering their respective signal transduction pathways. Nuclear run-off analyses suggest that post-transcriptional (rather than transcriptional) mechanisms are important in the accumulation of MUC2 mRNA. Finally, we show 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 different regulation of MUC2 in HT29 cells and in mucinous tumor cell lines may reflect molecular pathways that characterize colon carcinomas of different histology and pathology.

Original languageEnglish (US)
Pages (from-to)13956-13961
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number19
StatePublished - Jul 5 1993

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HT29 Cells
Mucins
Colforsin
Signal transduction
Genes
Cells
Carcinoma
Tumors
Acetates
Tetradecanoylphorbol Acetate
Signal Transduction
Histology
Butyric Acid
Pathology
Protein Kinase Inhibitors
Gene expression
Protein Kinase C
Goblet Cells
Staphylococcal Protein A
Tumor Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulated expression of an intestinal mucin gene in HT29 colonic carcinoma cells. / Velcich, Anna; Augenlicht, Leonard H.

In: Journal of Biological Chemistry, Vol. 268, No. 19, 05.07.1993, p. 13956-13961.

Research output: Contribution to journalArticle

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