Attenuated Expression of Xeroderma Pigmentosum Group C Is Associated with Critical Events in Human Bladder Cancer Carcinogenesis and Progression
| Autor: | Jin Li, Zhiwen Chen, Zhigang Xu, Bo Song, Jin Yang, Gan Wang |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty DNA Complementary Xeroderma pigmentosum DNA Repair DNA repair Apoptosis Biology Transfection medicine.disease_cause Cell Line Tumor medicine Humans Tumor Protein p73 Cisplatin Bladder cancer Tumor Suppressor Proteins Cell Cycle Nuclear Proteins Cancer medicine.disease DNA-Binding Proteins Cell Transformation Neoplastic Urinary Bladder Neoplasms Oncology Tumor progression Mutation Disease Progression Cancer research Tumor Suppressor Protein p53 Carcinogenesis HeLa Cells medicine.drug |
| Zdroj: | Cancer Research. 67:4578-4585 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. [Cancer Res 2007;67(10):4578–85] |
| Databáze: | OpenAIRE |
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