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Published on: June 18, 2015
Inactivation of the Tumor Suppressor CYLD Sensitizes Mice to Breast Cancer Development
Athanasios Pseftogas1, Konstantinos Xanthopoulos1,2,3, Athanasios Siasiaridis1
1School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Background/Aim:
Breast cancer is a leading cause of cancer-related deaths among women. Down-regulation of the tumor suppressor gene Cyld in breast cancer has been linked to a poor prognosis. This study investigated the role of Cyld in breast cancer using conditional mutant mouse models carrying a Cyld mutation, which inactivates the deubiquitinating activity of its protein product CYLD in mammary epithelial cells.
Materials And Methods:
We examined the potential of CYLD inactivation to induce mammary tumors spontaneously or modify the susceptibility of mice to mammary tumorigenesis by DMBA treatment or ErbB2 over-expression.
Results:
CYLD inactivation significantly increased susceptibility to breast cancer induced by either DMBA treatment or ErbB2 over-expression. Moreover, while CYLD inactivation alone did not lead to spontaneous mammary tumorigenesis, it did contribute to the formation of multifocal hyperplastic lesions in virgin mice of predominantly FVB/NJ background.
Conclusion:
Our study demonstrates the tumor enhancing potential of CYLD inactivation in mammary tumorigenesis in vivo and establishes novel relevant mouse models that can be exploited for developing prognostic and therapeutic protocols.
Insights
Inactivating the Cyld gene, a tumor suppressor, enhances breast cancer development in mice. This study introduces new mouse models for breast cancer research and therapy development.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Breast cancer remains a significant cause of mortality in women.
- Down-regulation of the Cyld tumor suppressor gene correlates with poor breast cancer prognosis.
- The deubiquitinating enzyme CYLD plays a role in cellular regulation.
Purpose of the Study:
- To investigate the role of Cyld gene inactivation in mammary tumorigenesis.
- To utilize conditional mutant mouse models to study Cyld function in vivo.
- To establish relevant models for breast cancer research.
Main Methods:
- Generation of conditional mutant mice with Cyld inactivated in mammary epithelial cells.
- Assessment of spontaneous mammary tumor development.
- Evaluation of susceptibility to chemically induced (DMBA) or genetically engineered (ErbB2 overexpression) mammary tumorigenesis.
Main Results:
- CYLD inactivation significantly increased susceptibility to DMBA-induced and ErbB2-overexpressing mammary tumors.
- CYLD inactivation alone did not cause spontaneous tumors but promoted hyperplastic lesions in specific mouse strains.
- These findings highlight the tumor-promoting role of CYLD inactivation in mammary tissue.
Conclusions:
- CYLD inactivation enhances mammary tumorigenesis in vivo.
- Novel mouse models were developed for studying breast cancer progression.
- These models can aid in developing prognostic and therapeutic strategies for breast cancer.
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