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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #172599
Title: THE EFFECT OF MODERATE FOLATE DEPLETION ON GENE EXPRESSION IN HUMAN COLONIC EPITHELIAL CELL LINES

Author
item CROTT, JIMMY - TUFTS/HNRCA
item KEYES, MARY - TUFTS/HNRCA
item Choi, Sang-Woon
item JANG, HYERAN - TUFTS/HNRCA
item Mason, Joel

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 11/15/2004
Publication Date: 4/1/2005
Citation: Crott, J.W., Keyes, M., Choi, S., Jang, H., Mason, J.B. 2005. The effect of moderate folate depletion on gene expression in human colonic epithelial cell lines. Federation of American Societies for Experimental Biology Conference. April 2-6, 2005. San Diego, CA. Abstract no. 994.

Interpretive Summary:

Technical Abstract: Folate is essential for DNA synthesis, repair and methylation. Folate deficiency may affect gene expression by disrupting DNA methylation or by inducing DNA breaks, gene deletions or gene amplification. These deleterious genetic and epigenetic changes may underlie the inverse relationship between folate status and the risk for colorectal cancer. We studied the expression of genes related to carcinogenesis, as well as genes involved in folate metabolism and oxidative phosphorylation, in colonic epithelial cell lines. HCEC (Nestle, Switzerland) and NCM460 (Incell, TX) cells were grown for 32 - 34 days in media containing 25, 50, 75 or 150 nM folic acid (FA). 25nM FA is a moderate level of depletion which supports proliferation at approximately half the rate of 150nM FA (replete). Gene expression was measured by fluorescent quantitative PCR with Taqman probes (ABI, CA) and normalized to GAPDH. FA depletion induced the up regulation (P<0.05) of urokinase (3.2x, 2.3x), p53 (2.1x, 1.2x) and folate receptor-alpha (5.2x, 9.6x) in HCEC and NCM460 (respectively). beta'catenin (1.5x) and Estrogen receptor-alpha (1.7x) were up regulated by FA depletion in NCM460 cells (p<0.05). APC, k-ras and cytochrome C oxidase subunit 1 were not affected by FA concentration. This data shows that FA depletion alters the expression of genes involved in carcinogenesis in colonic cells. Elevated p53 may be a response to uracil-induced DNA damage. We suggest that FA depletion may inhibit beta-catenin degradation and thereby stimulate the transcription of urokinase, p53 and estrogen receptor-alpha. Work is underway to further characterize the effect of FA depletion on genetic integrity and gene pathways.