Finkel-Biskis-Reilly Osteosarcoma Virus v-Fos Inhibits Adipogenesis and Both the Activity and Expression of CCAAT/Enhancer Binding Protein α, a Key Regulator of Adipocyte Differentiation*
- From the Departments of Cell Biology and Pathology and Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Abstract
Finkel-Biskis-Reilly (FBR) osteosarcoma virus v-Fos causes tumors of mesenchymal origin, including osteosarcomas, rhabdomyosarcomas, chondrosarcomas, and liposarcomas. Because the cell of origin in all these tumors is a pluripotent mesenchymal cell, the variety of tumors seen in mice which express FBR v-Fos implies that FBR v-Fos inhibits multiple differentiation pathways. To study the mechanism of FBR v-Fos’ inhibition of mesenchymal differentiation, we utilized an in vitro model of adipocyte differentiation. We show by both morphological and biochemical means that FBR v-Fos inhibits adipocyte differentiation in vitro. This inhibition is due to FBR v-Fos’ inhibition of the growth arrest characteristic of terminal differentiation and FBR v-Fos’ inhibition of the expression and activity of a key regulator of this growth arrest, C/EBPα. The in vitro inhibition of adipogenesis by FBR v-Fos has in vivo significance as immunostaining of FBR v-Fos-induced tumors shows no CCAAT/enhancer binding protein (EBP)-α expression. These data implicate C/EBPα as a protein involved in the generation of liposarcomas.
Footnotes
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↵* This work was supported in part by National Institutes of Health Public Service Grant RO1CA51735.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Supported by National Institutes of Health Public Health Service Medical Scientist Training Program Grant 523CMO734714.
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↵§ To whom correspondence should be addressed: 659 MRB II, 2220 Pierce Ave. South, Vanderbilt University Cancer Center, Nashville, TN 37232.
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↵1 The abbreviations used are: FBR v-Fos, Finkel-Biskis-Reilly osteosarcoma virus v-Fos; C/EBP, CCAAT/enhancer binding protein; CAT, chloramphenicol acetyltransferase;neo R, neomycin resistance gene; G3PDH, glycerol-3-phosphate dehydrogenase; EMSA, electrophoretic mobility shift assay; CRP, C-reactive protein; RSV, Rous sarcoma virus; MSV, murine sarcoma virus.
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↵2 D. W. Abbott and J. T. Holt, unpublished observations.
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- Received August 5, 1997.
- Revision received October 8, 1997.
