DIFFERENTIAL CELLULAR EXPRESSION OF THE HUMAN MSH2 REPAIR ENZYME IN SMALL AND LARGE-INTESTINE

The human MSH2 (hMSH2) protein is responsible for the initial recognit ion of mismatched nucleotides during the postreplication mismatch repa ir process. Loss of hMSH2 function has been demonstrated to lead to th e accumulation of replication errors, resulting in a mutator phenotype , which may be responsible for the multiple mutations required for mul tistage carcinogenesis, Alterations of the hMSH2 gene has been linked to approximately 60% of hereditary nonpolyposis colon cancer cases. Co lon tumors in hereditary nonpolyposis colon cancer patients originate within benign preneoplastic adenomas and display replication errors in the form of microsatellite instability, The aim of this study was to investigate the cellular expression of the hMSH2 protein in cells of t he large and small intestines. Using antibody specific for hMSH2, we h ave determined that this protein is highly expressed in cells of the c rypts of Lieberkuhn that are undergoing rapid renewal in both the ileu m and colon. Proliferative perifibroblasts in the colon also showed si gnificant presence of the hMSH2 protein, These results confirm the hyp othesis that hMSH2 is expressed in highly proliferative cells of the g ut, and mutations in this gene could, therefore, he expected to expedi te the progression of adenoma to carcinoma in this tissue.