Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation.
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 (alpha-D-glucopyranosyl-alpha-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.
Lu
X
X
Institute of Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Walker
T
T
MacManus
J P
JP
Seligy
V L
VL
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000235:genetics; D012313:RNA / Q000032:analysis*; D000077278:RNA, Mitochondrial; D012334:RNA, Neoplasm / Q000032:analysis*; D014158:Transcription, Genetic; D014199:Trehalose / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012334:RNA, Neoplasm; D012313:RNA; D014199:Trehalose; D009245:NADH Dehydrogenase