Attenuated expression of xeroderma pigmentosum group C is associated with critical events in human bladder cancer carcinogenesis and progression.
Xeroderma pigmentosum group C (XPC) is an important DNA damage recognition protein that binds to damaged DNA at a very early stage during DNA repair. The XPC protein is also involved in DNA damage-induced cell cycle checkpoint regulation and apoptosis. XPC defects are associated with many types of solid tumors. The mechanism of the XPC protein in cancer progression, however, remains unclear. In this report, we showed the strong correlation between bladder cancer progression and attenuated XPC protein expression using tissues derived from patients with bladder cancer. The results obtained from our immunohistochemical studies further revealed a strong correlation of XPC deficiency, p53 mutation, and the degree of malignancy of bladder tumors. In addition, the results obtained from our studies have also shown that HT1197 bladder cancer cells, which carry a low-level XPC protein, exhibited a decreased DNA repair capability and were resistant to cisplatin treatment. When an XPC gene cDNA-expression vector was stably transfected into the HT1197 cells, however, the cisplatin treatment-induced apoptotic cell death was increased. Increased p53 and p73 responses following cisplatin treatment were also observed in HT1197 cells stably transfected with XPC cDNA. Taken together, these results suggest that XPC deficiency is an important contributing factor in bladder tumor progression and bladder cancer cell drug resistance.
Chen
Zhiwen
Z
Urology Institute of People's Liberation Army, Southwest Hospital, The Third Military Medical University, Chongqing, P.R. China. zhiwen@mail.tmmu.com.cn
Yang
Jin
J
Wang
Gan
G
Song
Bo
B
Li
Jin
J
Xu
Zhigang
Z
D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D004260:DNA Repair; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D018450:Disease Progression; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000096:biosynthesis; D014162:Transfection; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C495901:TP53 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C086984:XPC protein, human; D002945:Cisplatin