A novel target cell for c-fos-induced oncogenesis: development of chondrogenic tumours in embryonic stem cell chimeras.
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.
Wang
Z Q
ZQ
Research Institute of Molecular Pathology (IMP), Vienna, Austria.
Grigoriadis
A E
AE
Möhle-Steinlein
U
U
Wagner
E F
EF
D000818:Animals; D015152:Blotting, Northern; D002356:Cartilage / Q000196:embryology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002678:Chimera; D002813:Chondrosarcoma / Q000235:genetics*; D003094:Collagen / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D007150:Immunohistochemistry; D051379:Mice; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012313:RNA / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D012313:RNA; D003094:Collagen; D011505:Protein-Tyrosine Kinases