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Differentiation of HT-29 Human Colonic Adenocarcinoma Cells Correlates with Increased Expression of Mitochondrial RNA: Effects of Trehalose on Cell Growth and Maturation¹

Institute of Biological Sciences, National Research Council of Canada, Ottawa, Ontario, K1A 0R6, Canada

The HT-29 human adenocarcinoma cell line has been used extensively in the study of colonic cell differentiation and colon cancer. We report here that substitution of glucose with trehalose (-D-glucopyranosyl--D-glucopyranoside) depresses growth and promotes mucin-producing, goblet-like maturation of HT-29. An initial characterization of this process was made by analyzing several cDNA clones whose RNA templates were differentially expressed at elevated levels in cells grown in trehalose-containing medium. Seven of the 9 clones examined corresponded to 6 mitochondrial genes whose expression levels, relative to those from glucose-grown cells, ranged from approximately 3-fold for 16S rRNA to 8–23-fold for NADH dehydrogenase subunit 4. On the other hand, levels of mitochondrial DNA copy, measured by using NADH dehydrogenase subunit 4 cDNA as probe, were shown to be unaffected by trehalose treatment. Elevation of cellular NADH dehydrogenase subunit 4 RNA in HT-29 cultures grown in medium containing different components (sodium butyrate, galactose, no-sugar, glucose, cellobiose) generally correlated with depressed growth levels and specifically with increased numbers of mucin-producing cells present. Like butyrate, the sugar, trehalose, is an effective inducer of HT-29 differentiation, and may prove useful as a dietary therapeutic, and as a probe for elucidating mitochondrial involvement in colonic cell differentiation and transformation.

¹ This is National Research Council of Canada publication 32005. Work was supported by IBS intramural research funds.

² To whom requests for reprints should be addressed, at Molecular Cell Biology Group, Institute of Biological Sciences, Building M-54, Room 2153, NRCC, Ottawa, Ontario, Canada K1A OR6.

Received 12/26/91. Accepted 4/20/92.

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