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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Attenuated expression of xeroderma pigmentosum group C is associated with critical events in human bladder cancer
Zhiwen Chen1, Jin Yang, Gan Wang
1Urology Institute of People's Liberation Army, Southwest Hospital, The Third Military Medical University, Chongqing, P.R. China. zhiwen@mail.tmmu.com.cn
Abstract:
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.
Insights
Xeroderma pigmentosum group C (XPC) protein deficiency correlates with bladder cancer progression and drug resistance. Restoring XPC levels in cancer cells enhances DNA repair and chemotherapy-induced apoptosis.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Xeroderma pigmentosum group C (XPC) is a key DNA damage recognition protein involved in DNA repair, cell cycle checkpoints, and apoptosis.
- XPC defects are linked to various solid tumors, but its precise role in cancer progression remains largely unknown.
Purpose of the Study:
- To investigate the correlation between XPC protein expression and bladder cancer progression.
- To elucidate the role of XPC in DNA repair, drug resistance, and apoptosis in bladder cancer cells.
Main Methods:
- Immunohistochemical analysis of XPC expression in bladder cancer tissues.
- Assessment of DNA repair capacity and cisplatin resistance in HT1197 bladder cancer cells with varying XPC levels.
- Stable transfection of XPC cDNA into HT1197 cells to restore XPC expression.
Main Results:
- A strong correlation was observed between attenuated XPC protein expression and bladder cancer progression.
- XPC deficiency was associated with p53 mutations and higher tumor malignancy.
- HT1197 cells with low XPC showed reduced DNA repair and cisplatin resistance, which was reversed upon XPC restoration.
- Restored XPC expression increased cisplatin-induced apoptosis and p53/p73 responses.
Conclusions:
- XPC deficiency is a significant factor in bladder tumor progression and contributes to drug resistance in bladder cancer cells.
- XPC plays a crucial role in maintaining DNA repair efficiency and chemosensitivity in bladder cancer.
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