A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice

Cancer Res. 2009 Apr 15;69(8):3657-64. doi: 10.1158/0008-5472.CAN-08-4127. Epub 2009 Apr 7.

Abstract

Previously, we reported modeling synovial sarcomas in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein in Myf5-expressing myoblasts. Using a tamoxifen-inducible CreER system in mice, we show here that sporadic expression of SYT-SSX2 across multiple tissue types leads to exclusive formation of synovial sarcoma-like tumors, whereas its widespread expression is lethal. Certain clinical and histologic features of tumors in this new model suggest additional nonmyoblast origin for synovial sarcoma. CreER-based sporadic expression both avoids the severe early developmental phenotypes associated with widespread SYT-SSX2 expression and better models natural pathogenesis of cancers in which transformed cells usually arise within an environment of largely normal cells. Furthermore, this strategy may recapitulate multiple potential cellular origins within a single model system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Integrases / genetics*
  • Mice
  • Oncogene Proteins, Fusion / biosynthesis
  • Oncogene Proteins, Fusion / genetics
  • Sarcoma, Synovial / genetics*
  • Sarcoma, Synovial / pathology*
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology*
  • Translocation, Genetic

Substances

  • Oncogene Proteins, Fusion
  • SYT-SSX fusion protein
  • Cre recombinase
  • Integrases