| First Author | Leclerc D | Year | 2013 |
| Journal | Mol Nutr Food Res | Volume | 57 |
| Issue | 4 | Pages | 686-97 |
| PubMed ID | 23001810 | Mgi Jnum | J:356522 |
| Mgi Id | MGI:7762614 | Doi | 10.1002/mnfr.201200212 |
| Citation | Leclerc D, et al. (2013) Differential gene expression and methylation in the retinoid/PPARA pathway and of tumor suppressors may modify intestinal tumorigenesis induced by low folate in mice. Mol Nutr Food Res 57(4):686-97 |
| abstractText | SCOPE: Inadequate folate intake increases risk for colorectal cancer. We previously showed that low-folate diets induced intestinal tumors in BALB/c mice, but not in C57BL/6 mice. We suggested that DNA damage, altered methylation, and reduced apoptosis could contribute to tumorigenesis in this model. METHODS AND RESULTS: To identify genes involved in tumorigenesis, we compared gene expression profiles in preneoplastic intestine of BALB/c and C57BL/6 mice-fed low folate. We identified 74 upregulated and 90 downregulated genes in BALB/c compared to C57BL/6 mice. We validated decreased expression of Bcmo1 and increased expression of Aldh1a, which would be expected to upregulate the peroxisome proliferator-activated receptor alpha (PPARA) pathway, and confirmed the expected upregulation of several Ppara downstream genes. We verified, in BALB/c mice, reduced expression of Sprr2a, a gene that increases resistance to oxidative damage, and of two oncosuppressors (Bmp5 and Arntl). Low folate increased Ppara and Aldh1a1 expression, and decreased Bcmo1, Sprr2a, and Bmp5 expression in BALB/c, compared to BALB/c on control diets. Bcmo1, Ppara, and Bmp5 showed differential DNA methylation related to strain, diet, and/or Mthfr genotype. CONCLUSION: Disturbed regulation of the retinoid/PPARA pathway, which influences oxidative damage, and altered expression of tumor suppressors may contribute to intestinal tumorigenesis induced by low-folate intake. |
