Elevated insulin receptor protein expression in experimentally induced colonic tumors

Insulin is associated with augmented colon carcinogenesis in vivo, but the mechanism(s) of growth promotion is not known. This study investigates the expression profile of a key component of the insulin signaling pathway, the insulin receptor (IR), in colonic tumors in comparison to normal colonic mucosa and the effects of dietary lipids. Male F344 rats harboring preneoplastic lesions were randomly allocated to three high fat diet groups: beef tallow (HFB), corn oil (HFC), fish oil (HFF) or a low fat corn oil (LFC) diet for 16 weeks. Colonic tumors and mucosae were analyzed for IR protein by Western blot and immunohistochemical analyses. IR mRNA expression was also analyzed by semi-quantitative RT-PCR. Western blot analysis demonstrated that IR protein level was significantly greater ( P≤0.001) in tumors than in normal-appearing mucosae in each diet group, and varied ( P≤0.001) among the tumors in the order HFF>LFC>HFB>HFC. Immunohistochemical assessment of the tumors as compared to the normal mucosa confirmed the elevated expression of IR protein in the tumor cells compared to normal mucosae. Immunoreactivity was noted in the nuclear compartment. In normal colonic mucosae, IR protein levels were lower ( P≤0.001) in the saturated fat diet group (HFB) than the three unsaturated fat diet groups (LFC, HFC and HFF). IR mRNA transcript levels did not differ between colonic tumors and mucosae, and no significant diet effect was observed. These results demonstrate that steady state levels of IR are elevated in colonic tumors above that of normal mucosae in vivo irrespective of the dietary lipid environment. However, the IR mRNA transcript levels did not reflect any significant diet effect and remained relatively steady between the tumor and normal mucosa, indicating altered post transcriptional regulation of IR in tumor tissues compared to normal mucosae.