Review
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World J Gastrointest Pathophysiol. Jun 15, 2012; 3(3): 71-79
Published online Jun 15, 2012. doi: 10.4291/wjgp.v3.i3.71
Molecular signaling mechanisms of apoptosis in hereditary non-polyposis colorectal cancer
Samar Hassen, Nawab Ali, Parimal Chowdhury
Samar Hassen, Nawab Ali, Department of Applied Science, College of Science and Mathematics, University of Arkansas, Little Rock, AR 72204, United States
Parimal Chowdhury, Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States
Author contributions: Hassen S performed experiments and participated in writing and drawings; Ali N and Chowdhury P conceived the idea and participated in writing.
Supported by NSF-EPSCoR P3 Center and NASA-EOSCoR Research Infrastructure Development Funds to Ali N
Correspondence to: Parimal Chowdhury, BS, MS, PhD, AGAF, Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 W Markham Street, Little Rock, AR 72205, United States. pchowdhury@uams.edu
Telephone: +1-501-6865443 Fax: +1-501-6868167
Received: October 17, 2011
Revised: May 31, 2012
Accepted: June 12, 2012
Published online: June 15, 2012
Abstract

Colorectal cancer is the second most leading cause of cancer related deaths in the western countries. One of the forms of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC), also known as “Lynch syndrome”. It is the most common hereditary form of cancer accounting for 5%-10% of all colon cancers. HNPCC is a dominant autosomal genetic disorder caused by germ line mutations in mismatch repair genes. Human mismatch repair genes play a crucial role in genetic stability of DNA, the inactivation of which results in an increased rate of mutation and often a loss of mismatch repair function. Recent studies have shown that certain mismatch repair genes are involved in the regulation of key cellular processes including apoptosis. Thus, differential expression of mismatch repair genes particularly the contributions of MLH1 and MSH2 play important roles in therapeutic resistance to certain cytotoxic drugs such as cisplatin that is used normally as chemoprevention. An understanding of the role of mismatch repair genes in molecular signaling mechanism of apoptosis and its involvement in HNPCC needs attention for further work into this important area of cancer research, and this review article is intended to accomplish that goal of linkage of apoptosis with HNPCC. The current review was not intended to provide a comprehensive enumeration of the entire body of literature in the area of HNPCC or mismatch repair system or apoptosis; it is rather intended to focus primarily on the current state of knowledge of the role of mismatch repair proteins in molecular signaling mechanism of apoptosis as it relates to understanding of HNPCC.

Keywords: Colorectal cancer; Hereditary non-polyposis colorectal cancer; Apoptosis; Molecular signaling mechanisms; DNA mismatch repair proteins