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MNNG诱发的遗传不稳定vero细胞中DNA体外复制保真度和错配修复功能的研究

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癌变．畸变．突变 1997年第6期9卷 348-349页

作者：余应年浙江医科大学病理生理教研室分子生物学实验室杭州31

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Mismatch repair genes (hMLH1, hPMS1, hPMS2, GTBP/hMSH6,HMSH2) in the pathogenesis of hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第20期11卷 3020-3026页

作者： Abdel-Rahman N. Zekri Gelane M. Sabry Abeer A. Bahnassy Kamal A. Shalaby Sabrin A.Abdel-Wahabh Serag Zakaria Virology and Immunology Unit Cancer Biology Department National Cancer Institute Cairo University Egypt Biochemistry Department Faculty of Science Ain Shams University Egypt Pathology Department National Cancer Institute Cairo University Egypt Tropical Medicine Department El-Kaser Al-Aini School of Medicine Cairo University Egypt

AIM: DNA misrnatch repair (MMR) is an impotent mechanism for maintaining fidelity of genomic DNA. Abnormalities in one or more MMR genes are implicated in the development of many cancers. We investigated the role of expression of MMR genes (hMLH1, hPMS1, hPMS2, GTBP/hMSH6, hMSH2) in hepatocellular carcinogenesis. METHODS: We evaluated the expression level of MMR genes in 33 hepatocellular carcinoma (HCC) cases using the multiplex reverse transcription (RT) PCR assays, as well as in 16 cases of normal adjacent hepatic tissues. Β-actin gene was used as an internal control and calibrator for quantification of gene expression. RESULTS: Out of the 33 studied cases, 25 were HCV positiveand 30 (90.9%) showed reduced expression in one or more of the studied MMR genes. Reduced expression was found in hMSH2 (71.9%), hMLH1 (53.3%), GTBP (51.1%), hPMS2 (33.3%) and hPMS1 (6%). A significant correlation was found between reduced expression of hPMS2(P= 0.0069) and GTBP(P= 0.0034), hPMS2and non-cirrhosis (P= 0.0197),hMLH1 and high grade. On the other hand, 57.1%, 50%, 20%, 18.8%, and 6% of the normal tissues distant to tumors showed reduced expression of hMSH2, hMLH1, GTBP, hPMS2, and hPMS1 respectively. Multivariate analysis revealed a significant correlation between the expression level of hMSH2(P= 0.008), hMLH1 (P= 0.001) and GTBP (P = 0.032)and HCC, between hPMS2, GTBP and HCVassociated HCC (P＜0.001, 0.002).CONCLUSION: Reduced expression of MMR genes seemsto play an important role in HCV-associated HCC. hPMS2 islikely involved at an early stage of hepatocarcinogenesis since it was detected in normal adjacent tissues. Reduced expression of hPMS2 provides a growth advantage and stimulates proliferation which encourages malignant transformation in non-cirrhotic HCV-infected patients via acquisition of more genetic damages.

关键词：错配基因基因修复 hMLH1 hPMS1 hPMS2 GTBP/hMSH6 hMSH2 肝细胞癌病理机制

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