Chen Zhiwen, Yang Jin, Wang Gan, Song Bo, Li Jin, Xu Zhigang
Urology Institute of People's Liberation Army, Southwest Hospital, The Third Military Medical University, Chongqing, P.R. China.
Cancer Res. 2007 May 15;67(10):4578-85. doi: 10.1158/0008-5472.CAN-06-0877.
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.
着色性干皮病C组（XPC）是一种重要的DNA损伤识别蛋白，在DNA修复的早期阶段就与受损DNA结合。XPC蛋白还参与DNA损伤诱导的细胞周期检查点调节和细胞凋亡。XPC缺陷与多种实体瘤相关。然而，XPC蛋白在癌症进展中的机制仍不清楚。在本报告中，我们使用膀胱癌患者的组织显示了膀胱癌进展与XPC蛋白表达减弱之间的强相关性。我们免疫组织化学研究的结果进一步揭示了XPC缺陷、p53突变与膀胱肿瘤恶性程度之间的强相关性。此外，我们研究的结果还表明，携带低水平XPC蛋白的HT1197膀胱癌细胞表现出DNA修复能力下降，并且对顺铂治疗具有抗性。然而，当将XPC基因cDNA表达载体稳定转染到HT1197细胞中时，顺铂治疗诱导的凋亡性细胞死亡增加。在用XPC cDNA稳定转染的HT1197细胞中，还观察到顺铂治疗后p53和p73反应增加。综上所述，这些结果表明XPC缺陷是膀胱肿瘤进展和膀胱癌细胞耐药性的一个重要促成因素。
