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Updated: Aug 14, 2026
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
High incidence of thymic epithelial tumors in E2F2 transgenic mice
Blanca Scheijen1, Marieke Bronk, Tiffany van der Meer
1Division of Molecular Carcinogenesis and Center for Biomedical Genetics, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands.
Abstract:
In virtually all human tumors, genetic and epigenetic alterations have been found which affect the INK4/-CYCLIN D/RB pathway, which regulates cell cycle entry and exit in normal cells. E2F transcription factors are important downstream components of this pathway, which act by controlling the expression of genes involved in DNA replication and cell cycle progression. To determine whether E2F2 deregulation promotes proliferation and tumorigenesis in vivo, we generated E2F2 transgenic mice, in which the Emu and murine pim1 promoter (pp) direct high expression of E2F2 in thymic epithelial cells. Emu-pp-E2F2 mice start to develop cytokeratin- and ER-TR4-positive cortical thymomas from the age of 20 weeks, and within 1 year, nearly all mice succumb to gross thymic epithelial tumors. General thymic morphology is largely maintained, but T cell development is perturbed in thymomas, with proportionately less CD4(+)CD8(+) double-positive thymocytes. In the first 3 months, E2F2 transgenic thymi exhibit only mild epithelial hyperplasia, and thereafter thymomas arise stochastically, probably following additional mutations. Interestingly, Emu-pp-E2F1 mice do not display cortical thymomas. These data argue that E2F2 promotes unscheduled cell division and oncogenic transformation of thymic epithelial cells.
Insights
Deregulation of E2F2 (a transcription factor) promotes thymic epithelial cell proliferation and tumor formation in mice. This suggests E2F2 plays a key role in tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The INK4/-CYCLIN D/RB pathway regulates cell cycle in normal cells.
- Genetic and epigenetic alterations in this pathway are common in human tumors.
- E2F transcription factors control genes for DNA replication and cell cycle progression.
Purpose of the Study:
- To investigate if E2F2 deregulation promotes proliferation and tumorigenesis in vivo.
- To understand the role of E2F2 in thymic epithelial cell transformation.
Main Methods:
- Generated E2F2 transgenic mice using the Emu and murine pim1 promoter (pp).
- High expression of E2F2 was directed in thymic epithelial cells.
- Observed tumor development and characterized thymic morphology and T cell development.
Main Results:
- E2F2 transgenic mice developed cortical thymomas from 20 weeks of age.
- Nearly all E2F2 transgenic mice succumbed to thymic epithelial tumors within 1 year.
- T cell development was perturbed in thymomas, with reduced CD4(+)CD8(+) thymocytes.
- Epithelial hyperplasia was observed early, with tumors arising stochastically later.
- E2F2 transgenic mice, but not E2F1 transgenic mice, developed cortical thymomas.
Conclusions:
- E2F2 promotes unscheduled cell division in thymic epithelial cells.
- E2F2 plays a significant role in the oncogenic transformation of thymic epithelial cells.
- E2F2 is implicated in the development of thymic epithelial tumors.
