Molecular mechanism of adenomatous polyposis coli-induced blockade of base excision repair pathway in colorectal carcinogenesis

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• 作者：Satya Narayan ; ^{snarayan@ufl.edu" class="auth_mail" title="E-mail the corresponding author} ; Ritika Sharma
• 关键词：Adenomatous polyposis coli ; Base excision repair ; DNA damage ; Colorectal carcinogenesis
• 刊名：Life Sciences
• 出版年：2015
• 出版时间：15 October 2015
• 年：2015
• 卷：139
• 期：Complete
• 页码：145-152
• 全文大小：1053 K

文摘

Colorectal cancer (CRC) is the third leading cause of death in both men and women in North America. Despite chemotherapeutic efforts, CRC is associated with a high degree of morbidity and mortality. Thus, to develop effective treatment strategies for CRC, one needs knowledge of the pathogenesis of cancer development and cancer resistance. It is suggested that colonic tumors or cell lines harbor truncated adenomatous polyposis coli (APC) without DNA repair inhibitory (DRI)-domain. It is also thought that the product of the APC gene can modulate base excision repair (BER) pathway through an interaction with DNA polymerase 尾 (Pol-尾) and flap endonuclease 1 (Fen-1) to mediate CRC cell apoptosis. The proposed therapy with temozolomide (TMZ) exploits this particular pathway; however, a high percentage of colorectal tumors continue to develop resistance to chemotherapy due to mismatch repair (MMR)-deficiency. In the present communication, we have comprehensively reviewed a critical issue that has not been addressed previously: a novel mechanism by which APC-induced blockage of single nucleotide (SN)- and long-patch (LP)-BER play role in DNA-alkylation damage-induced colorectal carcinogenesis.