Molecular signaling mechanisms of apoptosis in hereditary non-polyposis colorectal cancer.
Molecular signaling mechanisms of apoptosis in hereditary non-polyposis colorectal cancer.
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DOI：
10.4291/wjgp.v3.i3.71
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发表时间：
2012-06-15
期刊：
影响因子：
--
通讯作者：
Chowdhury, Parimal
中科院分区：
文献类型：
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作者：
Hassen, Samar;Ali, Nawab;Chowdhury, Parimal
结直肠癌是西方国家癌症相关死亡的第二大原因。结肠直肠癌的一种形式是遗传性非息肉病性结肠直肠癌（HNPCC），也称为“林奇综合征”。它是最常见的癌症遗传形式，占所有结肠癌的5%-10%。HNPCC是一种由错配修复基因突变引起的显性常染色体遗传病。人类错配修复基因在DNA的遗传稳定性中起着至关重要的作用，其失活导致突变率增加，并且通常丧失错配修复功能。最近的研究表明，某些错配修复基因参与了包括细胞凋亡在内的关键细胞过程的调控。因此，错配修复基因的差异表达，特别是MLH 1和MSH 2的贡献在对某些细胞毒性药物如顺铂的治疗抗性中起重要作用，顺铂通常用作化学预防。了解错配修复基因在细胞凋亡的分子信号机制中的作用及其在HNPCC中的作用需要进一步关注这一重要的癌症研究领域，本文旨在实现细胞凋亡与HNPCC的联系这一目标。目前的审查并不打算提供一个全面的枚举的整个身体的文献在该地区的HNPCC或错配修复系统或细胞凋亡，而是打算主要集中在目前的知识状态的错配修复蛋白的作用，细胞凋亡的分子信号机制，因为它涉及到理解HNPCC。
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.