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A novel target cell for c-fos-induced oncogenesis: development of chondrogenic tumours in embryonic stem cell
Z Q Wang1, A E Grigoriadis, U Möhle-Steinlein
1Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Abstract:
Embryonic stem (ES) cells were used to investigate the target cell specificity and consequences of c-fos when expressed ectopically during embryonic development. Chimeric mice generated with different ES cell clones selected for high exogenous c-fos expression were not affected during embryonic development; however, a high frequency of cartilage tumours developed as early as 3-4 weeks of age apparently independent of the extent of chimerism. The tumours originated from cartilagenous tissues and contained many chondrocytes. Expression of exogenous c-fos RNA and Fos protein was observed during development but was highest in tumour tissues, predominantly in differentiating chondrocytes. A number of primary and clonal tumour-derived cell lines were established which expressed high levels of c-fos, c-jun as well as the cartilage-specific gene type II collagen and which gave rise to cartilage tumours in vivo, some of which also contained bone. Interestingly, the levels of c-Fos and c-Jun appeared to be coordinately regulated in the cell lines as well as in chimeric tissues. Thus, we demonstrate that chondrogenic cells and earlier progenitors are specially transformed by Fos/Jun and therefore represent a novel mesenchymal target cell for c-fos overexpression.
Insights
Overexpressing c-fos in embryonic stem cells led to cartilage tumors in mice, identifying chondrogenic cells as a novel mesenchymal target for c-fos overexpression.
Area of Science:
- Developmental Biology
- Oncology
- Molecular Biology
Background:
- Embryonic stem (ES) cells are crucial for studying early development.
- The role of c-fos in embryonic development and tumorigenesis requires further investigation.
Purpose of the Study:
- To investigate the target cell specificity of c-fos during embryonic development.
- To determine the consequences of ectopic c-fos expression in chimeric mice.
Main Methods:
- Generation of chimeric mice using ES cells with high exogenous c-fos expression.
- Analysis of tumor development, histology, and gene expression in chimeric mice.
- Establishment and characterization of tumor-derived cell lines.
Main Results:
- Chimeric mice did not show developmental defects but frequently developed cartilage tumors.
- Tumors originated from cartilaginous tissues and expressed high levels of c-fos, c-jun, and type II collagen.
- Fos and Jun proteins were coordinately regulated in tumor tissues and cell lines.
Conclusions:
- Chondrogenic cells and their progenitors are specifically transformed by Fos/Jun.
- Ectopic c-fos overexpression identifies a novel mesenchymal target cell for oncogenesis.