Malignant transformation of a human fibroblast cell strain by transfection of a v-fes oncogene but not by transfection of a gag-human c-fes construct.
To determine whether the human c-fes gene, a homologue of the feline v-fes oncogene, can play a role in the malignant transformation of human fibroblasts, we transfected a near-diploid, infinite life span, growth factor-independent, human fibroblast cell strain, MSU-1.2, with plasmids carrying a fes gene along with a selectable marker. The fes gene was either the v-fes oncogene from the Gardner-Arnstein strain of feline sarcoma virus or a chimeric construct in which 835 base pairs representing exons 10-19 from the human c-fes proto-oncogene had been substituted for the corresponding feline sequence in the v-fes oncogene. The transfected cells were selected in appropriate medium, and a number of drug-resistant clones were isolated, and the progeny cells were assayed for fes expression by immunoprecipitation analysis. Six independent clones that expressed the v-fes protein and four that expressed the gag-c-fes protein were further characterized. The former exhibited anchorage independence and formed progressively growing, invasive, spindle cell sarcomas in athymic mice after only a short latency period. The latter strains were not anchorage independent and did not form tumors in athymic mice. These results show that the v-fes oncogene can malignantly transform an infinite life span human fibroblast cell strain, but the human c-fes gene cannot.
Lin
C
C
Department of Microbiology, Michigan State University, East Lansing 48824.
Wang
Q
Q
Maher
V M
VM
McCormick
J J
JJ
D000818:Animals; D015139:Blotting, Southern; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts; D015870:Gene Expression; D015750:Genes, gag; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051578:Proto-Oncogene Proteins c-fes; D011519:Proto-Oncogenes; D014162:Transfection; D014183:Transplantation, Heterologous
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496645:FES protein, human; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes