Impact of O6-methylguanine-DNA methyltransferase expression on the drug resistance of clear cell renal cell carcinoma

被引：4
作者：
Ge, Nan [1 ]
Guo, Liqiang [1 ]
Zhang, Jie [1 ]
Lin, Zhaomin [2 ]
Li, Yan [3 ]
Liu, Yuqiang [1 ]
Kong, Feng [2 ]
Fang, Xiaolei [1 ]
Zhao, Shengtian [1 ]
机构：
[1] Shandong Univ, Hosp 2, Dept Urol Surg, Jinan 250000, Peoples R China
[2] Shandong Univ, Hosp 3, Cent Res Lab, Jinan 250000, Peoples R China
[3] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Dept Radiol, Jinan, Peoples R China
来源：
JAPANESE JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 45卷 / 09期
关键词：
MGMT; clear cell renal cell carcinoma; alkylating agents; MULTIGENE METHYLATION ANALYSIS; PROMOTER METHYLATION; THERAPEUTIC RESPONSE; MGMT; REPAIR; CANCER; GENE; P53; O(6)-ALKYLGUANINE; TOBACCO;
D O I：
10.1093/jjco/hyv095
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The deoxyribonucleic acid-repair protein O-6-methylguanine-deoxyribonucleic acid methyltransferase is a major determinant of resistance of cells to various alkylating drugs. Its expression profile is different in different cancer types. Here, we studied the expression and function of O-6-methylguanine-deoxyribonucleic acid methyltransferase in clear cell renal cell carcinoma. The expression of O-6-methylguanine-deoxyribonucleic acid methyltransferase was evaluated in clear cell renal cell carcinoma tissues and cell lines by quantitative real-time polymerase chain reaction and immunohistochemistry. The relationship between O-6-methylguanine-deoxyribonucleic acid methyltransferase expression and clinicopathological characteristics was analyzed. To further investigate the function of O-6-methylguanine-deoxyribonucleic acid methyltransferase in clear cell renal cell carcinoma resistance to alkylating agents, siRNA targeting O-6-methylguanine-deoxyribonucleic acid methyltransferase were used to silence the O-6-methylguanine-deoxyribonucleic acid methyltransferase expression. We found that O-6-methylguanine-deoxyribonucleic acid methyltransferase is over-expressed in clear cell renal cell carcinoma tissues and cell lines. O-6-methylguanine-deoxyribonucleic acid methyltransferase expression is related with tumor progression in clear cell renal cell carcinoma patients. Up-regulation of O-6-methylguanine-deoxyribonucleic acid methyltransferase plays a critical role in primary resistance to alkylating agents. The overexpression of O-6-methylguanine-deoxyribonucleic acid methyltransferase contributes to resistance of clear cell renal cell carcinoma to standard chemotherapy. Our results have significance for understanding a new pathway of the development of drug resistance of clear cell renal cell carcinoma.
引用
收藏
页码：860 / 866
页数：7
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