Differential expression of TNF-α signaling molecules and ERK1 in distal and proximal colonic tumors associated with obesity

Abstract

Distal and proximal colon cancers have been recognized as two different disease types in human population. The environmental factors involved in the pathogenesis of the proximal and distal tumors also differ. The main objective of this study was to determine if obesity-augmented colonic tumors differ from each other if they are located in different regions of the colonic axis. Zucker obese rats were injected with azoxymethane (AOM) 10 mg/kg body weight/week for 2 weeks. The tumors appeared within 20 weeks. The highest proportion of the tumors was in the distal colon, and the number declined towards the splenic flexure. A number of proteins previously reported to be altered in tumor tissue were assessed in the present study in tumors appearing in proximal and distal regions. Distal colonic tumors had higher TNF-α R2, NF-κB, and IκBα levels than tumors of proximal origin. In contrast, IKKβ was decreased in the proximal tumors. Insulin receptor and insulin-like growth factor-1R were higher in distal tumors. The mitogen-activated protein kinase (ERK2) levels were similar in the tumor groups; however, the ERK1 was significantly higher in the distal tumor than in the proximal tumor. Our findings suggest that colon tumors induced by AOM in different colonic regions are different from each other with respect to differential expression of proteins and support the concept that these disease states could respond differently to tumor-promoting and inhibitory conditions. Moreover, these findings support the concept that cancer preventive or therapeutic agents need to be evaluated for their effectiveness on proximal as well as on distal tumors.