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Effect of FOS and JUN expression in inmortalized human mesenchymal progenitor cells

ABSTRACT: Mesenchymal progenitor cells (MPCs) have been proposed as cells of origin for sarcomas, while c-Fos and c-Jun transcription factors have been proposed has a oncogenes in sarcoma tumors. Here we study the effects of the induction of c-fos or c-Jun expression in immortalized hMPCs. C-Fos expression in these cells not only generated modifications in cell cycle, but also morphological changes, reduced mobility capacity and impaired adipogenic and osteogenic differentiation potentials. Even more interesting, c-Fos expressing immortalized hMPCs generated tumors with chondrogenic phenotype when implanted in immunodeficient mice. In accordance with these results, c-Fos is expressed at protein level in many human bone tumors, specifically in chondrosarcomas (76% c-fos positive samples) and osteosarcomas (49% c-fos positive samples). c-Jun expression in immortalized hMPCs induces increased proliferation and cell transformation and, once implanted in immunodeficient mice, these cells generate fibroblastic osteosarcomas. Doble c-jun and c-fos expression in immortalized hMPCs also induces cell transformation and yields high grade pleomorphic osteosarcoma tumors when implanted in immunodeficient mice.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79158 | GEO | 2018/07/17

REPOSITORIES: GEO

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miRNA expression profiles of HBE cells at different stages

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2009-12-31 | E-GEOD-19545 | biostudies-arrayexpress

Genome-wide mapping of Fos binding site (K562)

2009-12-31 | GSE19546 | GEO

Genome-wide mapping of Jun binding site (K562)

2009-12-31 | GSE19545 | GEO

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c-Fos mediates cell proliferation, invasion and drug-resistance of lung adenocarcinoma through MAPK signal pathway

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Project description:Cancer represents a complex family of diseases, characterized by the uncontrolled malignant growth of a particular cell type and by metastatic dissemination of these transformed cells to secondary sites. The hallmark tumor features emerge as a result of aberrant cellular signaling and pathological gene expression driven by cooperating genetic lesions. Being the convergence points of signaling pathways, transcription factors play crucial roles in cancer. Here, we define a transcription factor network that triggers an abnormal gene expression program promoting malignancy of clonal tumors, generated in Drosophila imaginal disc epithelium by overexpressing oncogenic Ras (RasV12) in a background lacking the tumor suppressor gene scribble (scrib1). We show that the nuclear receptor Ftz-F1 and the ETS-domain transcription factor Ets21c are upregulated in the rasV12scrib1 tumors in response to activated Jun-N-terminal kinase (JNK) signaling. Depletion of either Ftz-F1 or Ets21c improves viability of Drosophila larvae suffering from tumors, and this effect can be further enhanced by simultaneous removal of the Jun-dimerizing partner Fos. We identified Fos as a key mediator of JNK-induced differentiation defects and further show that Ftz-F1 and Fos are required for tumor invasiveness. However, only Ets21c can efficiently substitute for JNK and cooperate with RasV12 to induce invasive tumors that recapitulate hallmarks of malignant rasV12scrib1 tumors including elevated matrix metalloprotease (MMP1) and insulin-like peptide 8 (Dilp8) expression. In conclusion, our study provides functional evidence for a network of cooperating transcription factor that dictates target gene expression and promotes tumor phenotypes in response to aberrant JNK signaling. 20 samples analyzed, 4 control samples

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