INSULIN-LIKE GROWTH-FACTOR-I AND GROWTH-FACTOR-II RECEPTOR EXPRESSIONIN RAT COLON MUCOSE ARE AFFECTED BY DIETARY-LIPID INTAKE

Epidemiologic data and animal models have demonstrated a correlation b etween dietary fat composition and colon cancer risk. We have previous ly found that dietary fat alters cell proliferation in rat colon, whic h may influence the risk of colon cancer. Growth factors, including in sulin-like growth factor (IGF) I and II, regulate the cell cycle in mo st mammalian tissues. Hence, we measured IGF-I and IGF-II receptor exp ression in colonocytes from Sprague-Dawley rats fed diets containing e ither beef tallow (BT) or corn oil (CO) at 12, 30 or 37% of energy for 4 wk. Quantitative reverse transcriptase polymerase chain reaction (R T-PCR) using an internal standard was used to examine the relative exp ression of both IGF-I and II receptor mRNA in three sections of the co lon, The IGF-I receptor protein was also measured by Western immunoblo t. In the distal colon, IGF-I receptor gene expression and protein inc reased significantly as the percentage of CO increased. In both proxim al and middle colon, an increased percentage of BT resulted in signifi cantly increased IGF-II receptor expression. In the proximal colon, IG F-II receptor expression decreased with increasing CO concentration, w hereas in the middle colon, rats fed 37% CO had significantly higher I GF-II receptor expression than rats fed 12 or 30% CO, IGF-II receptor gene expression in proximal colon decreased with increased fat quantit y, independently of fat source, whereas in the middle colon, increased fat quantity resulted in increased IGF-II receptor expression. Thus I GF-I and IGF-II receptor mRNA and IGF-I receptor protein level in colo n mucosa were significantly altered by dietary fat source and quantity , thereby suggesting a potential influence of dietary fat on the endoc rine regulation of colon cell mitogenesis.