title: Suppression of transformed phenotype in hybrids of v-fgr and v-raf transformed rat-1 cells with rat embryonic fibroblasts is due to transcriptional inactivation of viral oncogenes.
abstract: Rat-1 cells that had been transformed to tumorigenicity by transfection with the retroviral oncogenes v-raf from 3611-murine sarcoma virus, or v-fgr from Gardner-Rasheed feline sarcoma virus were fused with rat embryonic fibroblasts at an early passage. In both fusion experiments hybrid cells were isolated that exhibited normal morphology, anchorage requirement for proliferation, and either no tumorigenicity (v-fgr) or extended latency periods for tumor growth (v-raf) in nude mice. Transcription of viral oncogenes is drastically reduced in hybrid cells (at least 30-fold compared to their transformed parental cells), while the half-life of the corresponding transcripts is not effected. In the chromatin of hybrid cells the integrated retroviral oncogenes are as sensitive to degradation with pancreatic DNase I as the endogenous actin gene. Thus the observed down regulation of proviral transcript levels does not correlate with changes in chromatin structure. We conclude that in hybrids of (v-fgr)- and (v-raf)-transformed Rat-1 cells with embryonic fibroblasts, transcription of the retroviral oncogenes appears to be repressed by trans-acting factors of the normal parental cell.
authors.affiliation: Institut für Genetik (Abt. Molekulargenetik), Universität Bonn, Federal Republic of Germany.
authors.forename: W
authors.initials: W
authors.lastname: Martin
authors.forename: E
authors.initials: E
authors.lastname: Lenz
authors.forename: B
authors.initials: B
authors.lastname: Grohé
authors.forename: K
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006822:Hybrid Cells / Q000166:cytology; D009857:Oncogenes; D010641:Phenotype; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000235:genetics*