Cell Growth & Differentiation, Vol 7, Issue 1 101-106, Copyright © 1996 by American Association of Cancer Research

ARTICLES

Steady-state levels of mitochondrial messenger RNA species characterize a predominant pathway culminating in apoptosis and shedding of HT29 human colonic carcinoma cells

BG Heerdt, MA Houston, JJ Rediske and LH Augenlicht
Department of Oncology, Albert Einstein Cancer Center, Bronx, New York 10467, USA.

A differentiated human colonic epithelial cell has undergone relatively stable molecular, biochemical, and cellular alterations resulting in the acquisition of structures, activities, and functions that characterize it as one of at least three mature phenotypes: a columnar absorptive, secretory, or enteroendocrine cell. We have shown previously that induction of HT29 cells with the short-chain fatty acid sodium butyrate elevates alkaline phosphatase activity, a marker of the absorptive cell phenotype, and increases mitochondrial gene expression. Furthermore, this induction is accompanied by subsequent apoptosis and cell shedding. In this report, we have investigated the effects of forskolin, a potent inducer of the MUC2 gene in HT29 cells, a marker of the secretory phenotype, and have shown that neither apoptosis nor mitochondrial gene expression are significantly stimulated. Thus, differentiation along the secretory cell lineage may not play a major role in apoptosis of colonic epithelial cells. Moreover, we have also investigated two polar solvents, DMSO and dimethylformamide, which have been reported to induce a more differentiated, but as yet not well characterized, phenotype in colonic carcinoma cells in culture. Although neither polar solvent induces alkaline phosphatase expression or MUC2 expression, both induce significant apoptosis, again associated with significant elevation of mitochondrial gene expression. Thus, elevation of mitochondrial gene expression appears to be an important pathway in the induction of apoptosis in colonic epithelial cells in culture, whether or not markers characteristic of differentiation along either the absorptive or secretory cell lineage are induced.

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