Colon cancer is one of the most frequently diagnosed cancers in the United States. Poor prognosis also makes it one of the deadliest cancers. Dietary factors are closely associated with tumorigenesis and development of colon cancer. Soy foods and soy bioactive components have been linked to lower colon cancer incidence in populations consuming large quantity of soy foods. However there are controversies and mechanisms by which soy products and soy bioactive components exert anticancer effects remain unknown. Because of lack of scientific evidence on the mechanisms of soy foods'cancer prevention potentials, there are no nutritional recommendations made to Americans. Based on current knowledge of colon cancer and preliminary data on beneficial actions of soy foods, the present proposal will test the hypothesis that dietary soy modulates colon cancer development through epigenetic programming at specific genes of WNT signaling pathway. An early maternal exposure model will be used for epigenetic programming by soy foods in colon of offspring rats. Using techniques including methylation analysis of CpG islands and chromatin immunoprecipitation coupled to a pathway-specific microarray, specific aims in this proposal include: 1) to identify specific genes along the WNT signaling pathway that are modified epigenetically by maternal soy diets;2) to determine the extent to which the WNT pathway is affected in colon in rats by soy foods;and 3) to monitor protection from getting colon cancer in later life of offspring rats with life long exposure to soy foods. Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and facilitate future experimental design for further research on soy foods and colon cancer prevention.
Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and aid future experimental design for further research on soy foods and colon cancer prevention. Data obtained will facilitate translational research in the future to define dietary recommendations for soy foods for American populations.
| Zhang, Yukun; Li, Qian; Zhou, Dan et al. (2013) Genistein, a soya isoflavone, prevents azoxymethane-induced up-regulation of WNT/ýý-catenin signalling and reduces colon pre-neoplasia in rats. Br J Nutr 109:33-42 |
| Wang, Huan; Li, Qian; Chen, Hong (2012) Genistein affects histone modifications on Dickkopf-related protein 1 (DKK1) gene in SW480 human colon cancer cell line. PLoS One 7:e40955 |
| Zhang, Yukun; Chen, Hong (2011) Genistein attenuates WNT signaling by up-regulating sFRP2 in a human colon cancer cell line. Exp Biol Med (Maywood) 236:714-22 |
| Zhou, Dan; Zhang, Yukun; Pan, Yuan-Xiang et al. (2011) Dickkopf homolog 1, a Wnt signaling antagonist, is transcriptionally up-regulated via an ATF4-independent and MAPK/ERK-dependent pathway following amino acid deprivation. Biochim Biophys Acta 1809:306-15 |
| Wang, Zuguang; Chen, Hong (2010) Genistein increases gene expression by demethylation of WNT5a promoter in colon cancer cell line SW1116. Anticancer Res 30:4537-45 |
