Insulin-Like Growth Factor-I and II Receptor Expression in Rat Colon Mucosa Are Affected by Dietary Lipid Intake

Abstract

Epidemiologic data and animal models have demonstrated a correlation between dietary fat composition and colon cancer risk. We have previously found that dietary fat alters cell proliferation in rat colon, which may influence the risk of colon cancer. Growth factors, including insulin-like growth factor (IGF) I and II, regulate the cell cycle in most mammalian tissues. Hence, we measured IGF-I and IGF-II receptor expression in colonocytes from Sprague-Dawley rats fed diets containing either beef tallow (BT) or corn oil (CO) at 12, 30 or 37% of energy for 4 wk. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using an internal standard was used to examine the relative expression of both IGF-I and II receptor mRNA in three sections of the colon. The IGF-I receptor protein was also measured by Western immunoblot. In the distal colon, IGF-I receptor gene expression and protein increased significantly as the percentage of CO increased. In both proximal and middle colon, an increased percentage of BT resulted in significantly increased IGF-II receptor expression. In the proximal colon, IGF-II receptor expression decreased with increasing CO concentration, whereas in the middle colon, rats fed 37% CO had significantly higher IGF-II receptor expression than rats fed 12 or 30% CO. IGF-II receptor gene expression in proximal colon decreased with increased fat quantity, independently of fat source, whereas in the middle colon, increased fat quantity resulted in increased IGF-II receptor expression. Thus IGF-I and IGF-II receptor mRNA and IGF-I receptor protein level in colon mucosa were significantly altered by dietary fat source and quantity, thereby suggesting a potential influence of dietary fat on the endocrine regulation of colon cell mitogenesis.

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