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- W3147657653 abstract "1375 Sphingolipid metabolites are generated to mediate the response of cells to growth factors, cytokines, cellular stresses, and chemotherapeutic agents. They regulate cell growth, and induce differentiation and apoptosis. These processes are deregulated in cancer cells but may be restored by exogenous sphingolipids. We have shown earlier that supplementation of the diet with sphingolipids that are hydrolyzed throughout the intestinal tract to bioactive metabolites reduced tumor incidence in DMH-treated mice by 70%. A reversal of carcinogen-induced changes in proliferation and cell death rather than the induction of apoptosis in transformed cells per se appeared to be a key event in this inhibition. However, the mechanisms of this growth ’normalization’ are not known. The present study was designed to identify targets of dietary sphingolipids in vivo in order to determine sphingolipid-modulated signaling pathways that lead to a suppression of tumor formation. The epithelial cells lining the colon were scraped from snap-frozen colons from control mice (fed only sphingolipid-free AIN76A diet) or sphingolipid-fed mice, and used for both RT-PCR analysis of gene transcription, and Western Blot analysis of protein expression. Proteins that have been shown to be involved in the regulation of cell growth by sphingolipids in vitro such as bax, bcl-2, c-myc, and proteins that are important in colon cancer and may be modulated by dietary sphingolipids such as Cyclin D1 and β-catenin were selected for these analyses. The transcription of most of these genes was not altered by feeding sphingomyelin for 47 weeks as determined by RT-PCR. However, the expression of key proteins such as β-catenin and Cyclin D1 was markedly reduced. These results suggest that a post-translational regulation of protein expression may be important in the regulation of colonic cell growth and tumor suppression by dietary sphingolipids. (Supported by the National Dairy Council)" @default.
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- W3147657653 date "2004-04-01" @default.
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- W3147657653 title "In vivo targets of dietary sphingolipids" @default.
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