Malignant transformation of NIH 3T3 fibroblasts by human c-sis is dependent upon the level of oncogene expression.
High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts. Clones with various levels of c-sis expression were generated by transfecting NIH 3T3 cells with a plasmid that expressed the human c-sis cDNA and the TN5 neomycin-resistance gene. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. Alterations in the phenotype of the clones that expressed c-sis ranged from increased growth in soft agar to malignant tumor formation in nude and syngeneic mice. Increased levels of c-sis cDNA expression correlated with the acquisition of features of transformation in a dose-dependent manner and altered the cellular phenotype in a manner consistent with the progression of cells towards malignancy. These data support a model in which low levels of sis gene expression in tumors contribute to the acquisition of some features of transformation but require complementation by other genes or factors to produce a fully malignant phenotype.
MacArthur
L H
LH
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892.
Clarke
M F
MF
Westin
E H
EH
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002999:Clone Cells; D006801:Humans; D019868:Kanamycin Kinase; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology; D010770:Phosphotransferases / Q000096:biosynthesis / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013997:Time Factors
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011993:Recombinant Fusion Proteins; D010770:Phosphotransferases; D019868:Kanamycin Kinase; D011505:Protein-Tyrosine Kinases