Differential Cellular Expression of the Human MSH2 Repair Enzyme in Small and Large Intestine

Teresa M. Wilson, Mark R. Kelley, Teresa M. Wilson, Mark R. Kelley, John R. Duguid, John N. Eble, Amy Ewel, Mary Kay Lescoe, Richard Fishel

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73 Scopus citations

Abstract

The human MSH2 (hMSH2) protein is responsible for the initial recognition of mismatched nucleotides during the postreplication mismatch repair process. Loss of hMSH2 function has been demonstrated to lead to the accumulation of replication errors, resulting in a mutator phenotype, which may he responsible for the multiple mutations required for multistage carcinogenesis. Alterations of the hMSH2 gene has been linked to approximately 60% of hereditary nonpolyposis colon cancer cases. Colon lemurs 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 the large and small intestines. Using antibody specific for hMSH2, we have determined that this protein is highly expressed in cells of the crypts of Lieberkuhn that are undergoing rapid renewal in both the ileum and colon. Proliferative perifibroblasts in the colon also showed significant presence of the hMSH2 protein. These results confirm the hypothesis that hMSH2 is expressed in highly proliferative cells of the gut, and mutations in this gene could, therefore, be expected to expedite the progression of adenoma to carcinoma in this tissue.

Original languageEnglish (US)
Pages (from-to)5146-5150
Number of pages5
JournalCancer Research
Volume55
Issue number22
StatePublished - Nov 15 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wilson, T. M., Kelley, M. R., Wilson, T. M., Kelley, M. R., Duguid, J. R., Eble, J. N., Ewel, A., Lescoe, M. K., & Fishel, R. (1995). Differential Cellular Expression of the Human MSH2 Repair Enzyme in Small and Large Intestine. Cancer Research, 55(22), 5146-5150.