Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/9136
c-Fos induces chondrogenic tumor formation in immortalized human mesenchymal progenitor cells
Abarrategi, Ander ISCIII | Gambera, Stefano ISCIII | Alfranca, Arantzazu ISCIII | Rodriguez-Milla, Miguel A ISCIII | Perez-Tavarez, Raquel ISCIII | Rouault-Pierre, Kevin | Waclawiczek, Alexander | Chakravarty, Probir | Mulero, Francisca CNIO | Trigueros, César | Navarro, Samuel | Bonnet, Dominique | Garcia-Castro, Javier ISCIII
Sci Rep. 2018 Oct 23;8(1):15615.
Mesenchymal progenitor cells (MPCs) have been hypothesized as cells of origin for sarcomas, and c-Fos transcription factor has been showed to act as an oncogene in bone tumors. In this study, we show c-Fos is present in most sarcomas with chondral phenotype, while multiple other genes are related to c-Fos expression pattern. To further define the role of c-Fos in sarcomagenesis, we expressed it in primary human MPCs (hMPCs), immortalized hMPCs and transformed murine MPCs (mMPCs). In immortalized hMPCs, c-Fos expression generated morphological changes, reduced mobility capacity and impaired adipogenic- and osteogenic-differentiation potentials. Remarkably, immortalized hMPCs or mMPCs expressing c-Fos generated tumors harboring a chondrogenic phenotype and morphology. Thus, here we show that c-Fos protein has a key role in sarcomas and that c-Fos expression in immortalized MPCs yields cell transformation and chondrogenic tumor formation.
Animals | Carcinogenesis | Cell Line | Cell Transformation, Neoplastic | Gene Expression Regulation, Neoplastic | Genes, fos | Humans | Mesenchymal Stem Cells | Mice | Mice, Inbred NOD | Mice, SCID | Proto-Oncogene Proteins c-fos | Sarcoma
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