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A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice
Malay Haldar1, Matthew L Hedberg, Matthew F Hockin
1Department of Human Genetics, University of Utah, School of Medicine, Salt Lake City, Utah 84112, USA.
Cancer Research
|April 9, 2009
Summary
Sporadic expression of the SYT-SSX2 fusion protein in mice exclusively forms synovial sarcoma-like tumors. This targeted approach avoids lethality and models cancer development in a more natural cellular environment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Synovial sarcoma is a rare soft tissue sarcoma characterized by the specific t(X;18) chromosomal translocation.
- Previous models involved constitutive expression of the SYT-SSX fusion protein in specific cell types.
Purpose of the Study:
- To develop a more refined mouse model for synovial sarcoma using conditional and sporadic gene expression.
- To investigate the impact of expression timing and distribution of the SYT-SSX2 fusion protein on tumor development and potential cellular origins.
Main Methods:
- Utilized a tamoxifen-inducible CreER system in mice for conditional and sporadic expression of the human SYT-SSX2 fusion protein.
- Expressed SYT-SSX2 in Myf5-expressing myoblasts and across multiple tissue types to observe tumor formation and developmental effects.
Main Results:
- Sporadic SYT-SSX2 expression led to exclusive formation of synovial sarcoma-like tumors, while widespread expression was lethal.
- Tumor characteristics suggested potential non-myoblast origins for synovial sarcoma.
- Conditional expression avoided severe developmental phenotypes and better mimicked natural cancer pathogenesis.
Conclusions:
- Conditional, sporadic expression of SYT-SSX2 provides a viable model for studying synovial sarcoma development.
- This model allows for investigation of multiple potential cellular origins of synovial sarcoma.
- The approach better reflects the in vivo microenvironment of cancer development.
