Dietary Carbohydrate Source Alters Gene Expression Profile of Intestinal Epithelium in Mice

Abstract

High-sucrose consumption is associated with increased risk of human colon cancer. Our previous research indicated that high-sucrose diets (vs. cornstarch) promote intestinal epithelial cell proliferation and tumorigenesis as well as increase serum glucose and hepatic IGF-I mRNA levels in APC ^Min mice. To examine the role of functional pathways, in particular of IGF-I signaling, in sucrose-induced intestinal epithelial cell proliferation and tumorigenesis, we examined the effects of dietary carbohydrate source (sucrose vs. cornstarch) on gene expression in the intestinal epithelium using cDNA microarray and quantitative RT-PCR analysis. Dietary carbohydrate source significantly ( P < 0.05) altered mRNA expression of 109 known genes in the small intestinal epithelium, including many involved in metabolic pathways. Consumption of high-sucrose diets altered expression levels of genes involved in cell adhesion, cell cycle control, and transduction signaling, consistent with increased risk of intestinal tumorigenesis. High-sucrose intake also affected expression of genes involved in IGF-I signaling, including upregulating IGF-II and downregulating IGFBP3, which supports our hypothesis that IGF-I signaling could play a role in intestinal epithelial cell proliferation and tumorigenesis promoted by high-sucrose consumption.

ACKNOWLEDGMENTS

The authors thank International Life Science Institute, North America, for financial support of this research via an Alex Malaspina Future Leader Award to L. D. Bourquin. Appreciation also is extended to Crystal Ybarra, Elizabeth Rondini, and Stephanie Maczka for assistance with animal care and tissue collection. Special thanks are extended to Ajith Vengellur and Kang Ae Lee for their generous help with the microarray analysis. Thanks are also extended to Drs. Ming Yi and Robert M. Stephens at the Advanced Biomedical Computing Center (NCI-Frederick/SAIC-Frederick, Inc., Frederick, MD) for pathway analysis of the microarray data. Bing Wang currently is affiliated with the Beckman Research Institute at the City of Hope National Medical Center, Los Angeles, CA 91010. Gerd Bobe is currently a fellow in the Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. John J. LaPres and Leslie D. Bourquin also are affiliated with the National Food Safety and Toxicology Center, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824.

Notes

^a Composition of AIN 93-MX mineral mix and AIN 93-VX vitamin as described in Reeves et al. (16).

^a Abbreviations are as follows: PCR, polymerase chain reaction; bp, base pairs; IGF-I, insulin-like factor I; IGF-II, insulin-like growth factor II; IGFBP3, insulin-like growth factor binding protein 3; PCNA, proliferating cell nuclear antigen; PIK3C2A, phosphatidylinositol 3-kinase, C2 domain containing, alpha polypeptide.

^a The functional grouping is based on GoMiner.

^a Abbreviation is as follows: PKC, protein kinase C.

^a Abbreviations are as follows: PCR, polymerase chain reaction; SEM, standard error of the mean; IGF-II, insulin-like growth factor II; IGFBP3, insulin-like growth factor binding protein 3; PCNA, proliferating cell nuclear antigen; PIK3C2A, phosphatidylinositol 3-kinase, C2 domain containing, alpha polypeptide; IGF-I, insulin-like factor I.

^a Abbreviations are as follows: PCR, polymerase chain reaction; SEM, standard error of the mean; IGF-II, insulin-like growth factor II; IGFBP3, insulin-like growth factor binding protein 3; PCNA, proliferating cell nuclear antigen; PIK3C2A, phosphatidylinositol 3-kinase, C2 domain containing, alpha polypeptide; IGF-I, insulin-like factor I.