A recessive cellular mutation in v-fes-transformed mink cells restores contact inhibition and anchorage-dependent growth.
A contact-inhibited revertant of mink cells transformed by the Gardner-Arnstein strain of feline sarcoma virus was isolated by fluorescence-activated sorting of cells stained with the mitochondria-specific dye rhodamine 123. The revertant cell line exhibited a decrease in its proliferative rate and saturation density and a complete loss of its capacity for anchorage-independent growth, but it remained tumorigenic when inoculated into nude mice. The revertant cells retained a rescuable Gardner-Arnstein feline sarcoma provirus, expressed high levels of the v-fes oncogene product and its associated tyrosine kinase activity, manifested elevated levels of phosphotyrosine-containing cellular proteins similar to those observed in v-fes-transformed cells, and were refractory to retransformation by retroviruses containing the v-fes, v-fms, and v-ras oncogenes. Fusion of the revertant and parental cells generated somatic cell hybrids which formed colonies in semisolid medium, indicating that the block in transformation was recessive. These data together with the observation that the revertant phenotype is unstable in continuous culture suggest that the loss of transformation is due to the presence of limiting quantities of a gene product which functions downstream of the v-fes-coded kinase in the mitogenic pathway.
Haynes
J R
JR
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Downing
J R
JR
D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D003260:Contact Inhibition; D015683:Gene Products, gag; D005808:Genes, Recessive; D008175:Lung Neoplasms / Q000032:analysis / Q000503:physiopathology; D008907:Mink; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D011533:Proviruses / Q000235:genetics; D012191:Retroviridae Proteins / Q000032:analysis* / Q000235:genetics; D012513:Sarcoma, Experimental / Q000032:analysis / Q000503:physiopathology; D014412:Tumor Virus Infections
D015683:Gene Products, gag; D012191:Retroviridae Proteins; D011505:Protein-Tyrosine Kinases