title: Impact of O6-methylguanine-DNA methyltransferase expression on the drug resistance of clear cell renal cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology Surgery, The Second Hospital, Shandong University, Jinan.
authors.forename: Nan
authors.initials: N
authors.lastname: Ge
authors.affiliation: Department of Urology Surgery, The Second Hospital, Shandong University, Jinan.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Urology Surgery, The Second Hospital, Shandong University, Jinan.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Central Research Laboratory, The Second Hospital, Shandong University, Jinan.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Radiology, The Affiliated Hospital, Shandong University of Traditional Chinese Medicine, Jinan, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Urology Surgery, The Second Hospital, Shandong University, Jinan.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Central Research Laboratory, The Second Hospital, Shandong University, Jinan.
authors.forename: Feng
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Urology Surgery, The Second Hospital, Shandong University, Jinan.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Urology Surgery, The Second Hospital, Shandong University, Jinan zhaoshengtian@sdu.edu.cn.
authors.forename: Shengtian
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019853:O(6)-Methylguanine-DNA Methyltransferase
keywords: MGMT; alkylating agents; clear cell renal cell carcinoma