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Cancer Cell. 2003 Dec;4(6):477-82.

Rhabdomyosarcoma development in mice lacking Trp53 and Fos: tumor suppression by the Fos protooncogene.

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1
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.

Abstract

The Fos protein, a major component of the AP-1 transcription factor, is essential for osteoclast differentiation, acts as an oncogene, potentiates transforming signals, and controls invasive growth and angiogenesis during tumor progression. To investigate a potential genetic interaction between the Trp53 and Fos pathways, Trp53/Fos double knockout mice were generated. These mice develop highly proliferative and invasive rhabdomyosarcomas of the facial and orbital regions, with more than 90% penetrance at 6 months of age. Rhabdomyosarcoma cell lines established from the primary tumors express characteristic muscle-specific markers, and reexpression of Fos is associated with enhanced apoptosis in vitro. Moreover, Fos is able to repress Pax7 expression in rhabdomyosarcoma cell lines and primary myoblasts, suggesting a molecular link to genetic alterations involved in human rhabdomyosarcomas.

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PMID:
14706339
DOI:
10.1016/s1535-6108(03)00280-0
[Indexed for MEDLINE]
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