Paired human fibrosarcoma cell lines that possess or lack endogenous mutant N-ras alleles as experimental model for Ras signaling pathways.
We present here a human cell model for examination of mutant N-ras function. The HT1080 human fibrosarcoma cell line is pseudodiploid and contains a single endogenous mutant N-ras allele. MCH603c8 cells are a variant of HT1080 cells, in which the mutant allele has been deleted. The two cell lines differ dramatically in the constitutive levels of activation of downstream members of the Ras signaling pathways, and in biological features of transformation and tumorigenicity. Downregulation or activation of individual Ras-dependent pathways can be accomplished via transfection of dominant negatives or activated mutant cDNAs into HT1080 and MCH603c8 cells, respectively. The biochemical and biological consequences of expression of these mutant cDNAs can be assessed. There are dramatic effects on both the transformed and tumorigenic phenotype, depending on the cell line and mutant cDNA that is transfected.
Gupta
S
S
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697-4025, USA.
Stanbridge
E J
EJ
D000199:Actins / Q000378:metabolism; D000483:Alleles; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis; D005354:Fibrosarcoma; D017353:Gene Deletion; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D016296:Mutagenesis; D010641:Phenotype; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
D000199:Actins; D018076:DNA, Complementary; D011494:Protein Kinases; D018631:ras Proteins