Finkel-Biskis-Reilly osteosarcoma virus v-Fos inhibits adipogenesis and both the activity and expression of CCAAT/enhancer binding protein alpha, a key regulator of adipocyte differentiation.
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/EBPalpha. 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)-alpha expression. These data implicate C/EBPalpha as a protein involved in the generation of liposarcomas.
Abbott
D W
DW
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Holt
J T
JT
D016475:3T3 Cells; D000273:Adipose Tissue / Q000166:cytology / Q000254:growth & development*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000502:physiology*; D012516:Osteosarcoma / Q000473:pathology / Q000821:virology*; D012190:Retroviridae / Q000235:genetics*; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016761:Oncogene Proteins v-fos