v-FBR-fos oncogene fails to rescue mammalian cells from growth arrest but affects the responses of human fibroblasts to heparin.
The effects of v-fos oncogene on the proliferation of mammalian cells were studied using several approaches. Constitutive overexpression of v-FBR-fos in normal human fibroblasts (MRC-5) and of v-FBR-fos in human chondrocytes (HAC21) failed to immortalise them, extend their in vitro lifespan, increase their growth rates or induce cellular transformation. Further, v-FBR-fos did not render MRC-5 growth factor-independent or alter their responsivenness to serum, but it markedly suppressed their heparin-induced proliferation. A conditionally immortalized, temperature-sensitive rat embryo fibroblast cell line (tsa14) which undergoes growth arrest upon inactivation of a thermolabile SV40 large T antigen by a temperature shift producing a phenotype that mimmicks the senescent phenotype, was also used to study the effects of v-FBR-fos on cell proliferation. Whereas a wild-type SV40 large T antigen rescued tsa14 from a temperature-dependent growth arrest, v-FBR-fos failed to do so. Hence, v-FBR-fos was not sufficient to, at least, complement the tsa14 growth defect. There was no change in the expression of c-jun and junB, members of the AP-1 transcriptional complex in MRC-5v-fos cells. These data show that v-FBR-fos is not sufficient to rescue mammalian cells from senescence but it can affect the responses of human fibroblasts to heparin suggesting a role of fos in cell proliferation.
Kolettas
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Cell and Molecular Physiology Unit, Laboratory of Experimental Physiology, University of Ioannina School of Medicine, 45110 Ioannina, Greece. ekoletas@cc.uoi.gr
Evangelou
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Gonos
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D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016922:Cellular Senescence; D005347:Fibroblasts / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D016761:Oncogene Proteins v-fos / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D009053:Sarcoma Viruses, Murine; D014162:Transfection
D016761:Oncogene Proteins v-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D006493:Heparin