Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #213922
Title: Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling, and folate uptake in human colonic epithelial cell lines

Author
item CROTT, JIMMY - TUFTS/HNRCA
item LIU, ZHENHUA - TUFTS/HNRCA
item KEYES, MARY - TUFTS/HNRCA
item Choi, Sang-Woon
item JANG, HYERAN - TUFTS/HNRCA
item MOYER, MARY PAT - INCELL CORP, TEXAS
item Mason, Joel

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2007
Publication Date: 5/1/2008
Citation: Crott, J.W., Liu, Z., Keyes, M.K., Choi, S., Jang, H., Moyer, M., Mason, J.B. 2008. Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling, and folate uptake in human colonic epithelial cell lines. Journal of Nutritional Biochemistry. 19(5):328-335.

Interpretive Summary: The B-vitamin folate is essential for maintaining the stability of our genetic material and is protective against several human cancers. In attempt to more fully understand the inverse relationship between folate intake and cancer risk, we studied the expression of several genes involved in processes that are commonly perturbed in cancer.

Technical Abstract: Folate deficiency may affect gene expression by disrupting DNA methylation patterns or by inducing base substitution, DNA breaks, gene deletions and gene amplification. Changes in expression may explain the inverse relationship observed between folate status and risk of colorectal cancer. Three cell lines derived from the normal human colon; HCEC, NCM356 and NCM460, were grown for 32 - 34 days in media containing 25, 50, 75 or 150 nM folic acid and the expression of genes involved in cell-cycle checkpoints, intracellular signaling, folate uptake and cell adhesion and migration was determined. Expression of Folate Receptor 1 was increased with decreasing media folate in all cell lines, as was p53, p21, p16 and '-catenin. With decreasing folate, E-cadherin and SMAD-4 expression were both decreased in NCM356. APC was elevated in NCM356 but unchanged in the other lines. No changes in global methylation were detected. A significant increase in p53 exon 7-8 strand breaks was observed with decreasing folate in NCM460 cells. The changes observed are consistent with DNA damage-induced activation of cell cycle checkpoints and cellular adaptation to folate depletion. Folate depletion-induced changes in the Wnt/APC pathway and also in genes involved in cell adhesion, migration and invasion may underlie observed relationships between folate status and cancer risk.