Journal
JAPANESE JOURNAL OF CLINICAL ONCOLOGY
Volume 45, Issue 9, Pages 860-866Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jjco/hyv095
Keywords
MGMT; clear cell renal cell carcinoma; alkylating agents
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Funding
- Shandong Province Natural Science Foundation [Y2008C14]
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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.
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