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Updated: Aug 29, 2026
An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Expression and regulation of tumor suppressor gene maspin in human bladder cancer
Shuji Sugimoto1, Nicolai Maass, Yukie Takimoto
1Department of Urology, University of Kiel, Arnold-Heller-strasse 7, Kiel 24105, Germany.
Abstract:
Maspin is a member of serine protease inhibitor family with tumor suppressing activity for breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of maspin in human bladder cancer. We evaluated maspin expression in 65 series of bladder cancer samples (22 transurethral resection (TUR) and 43 radical cystectomy) and studied the regulatory mechanism of maspin gene activation in bladder cancer cells. Maspin expression was immunohistochemically detected in four (18.2%) patients with TUR and 22 (51.2%) patients with radical cystectomy whereas no expression was observed in normal transitional cells located at tumor-free area in bladder. The maspin expression was significantly correlated with the development of muscle invasive bladder cancer (P=0.00008). Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive bladder cancer cell lines as well as maspin-negative RT4 cells. Furthermore, treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin in RT4 cells. Our results indicate that maspin may contribute to bladder cancer development and that DNA methylation and histone deacetylation may be important for regulating maspin gene activation in bladder cancer cells.
Insights
Maspin, a tumor suppressor, is expressed in bladder cancer, particularly in muscle-invasive types. Its gene activation in bladder cancer cells is regulated by DNA methylation and histone deacetylation.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Maspin, a serine protease inhibitor, exhibits tumor-suppressing properties in breast and prostate cancers by inhibiting invasion and metastasis.
- The role of maspin in human bladder cancer remains largely unexplored.
- Understanding maspin's function in bladder cancer is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate maspin expression in human bladder cancer tissues.
- To elucidate the regulatory mechanisms governing maspin gene activation in bladder cancer cells.
Main Methods:
- Immunohistochemical analysis of maspin expression in 65 bladder cancer samples (transurethral resection and radical cystectomy).
- Luciferase reporter assay to assess maspin promoter activity.
- Treatment of bladder cancer cell lines with DNA methyltransferase and histone deacetylase inhibitors to evaluate maspin re-expression.
Main Results:
- Maspin expression was detected in a subset of bladder cancer patients, with higher prevalence in radical cystectomy samples compared to transurethral resection.
- Maspin expression significantly correlated with the development of muscle-invasive bladder cancer.
- Maspin promoter activity was observed in both maspin-positive and -negative bladder cancer cell lines.
- Inhibition of DNA methylation and histone deacetylation led to maspin re-expression in maspin-negative bladder cancer cells.
Conclusions:
- Maspin expression is associated with bladder cancer progression, particularly muscle invasion.
- Epigenetic mechanisms, including DNA methylation and histone deacetylation, play a significant role in regulating maspin gene expression in bladder cancer.
- Maspin may contribute to bladder cancer development, warranting further investigation into its therapeutic potential.
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