Molecular and functional analysis of tumor-suppressor genes by transfection.
The transformed and tumorigenic phenotype of H-ras transfected rat FE-8 cells can be suppressed by cell fusion with normal rat embryo fibroblasts. Transfection into FE-8 cells of DNA prepared from normal human placenta followed by selective elimination of tumorigenic transfected cell clones resulted in the isolation of phenotypically normal revertants. These cells exhibited a fibroblastlike, normal morphology; were anchorage-dependent; and were unable to proliferate in medium with reduced serum concentrations. Their tumorigenicity was also reduced. The suppressed phenotype has been transferred in a second transfection cycle. Human repetitive DNA sequences were detected in secondary transfectant DNA. A putative human suppressor gene, designated NTS-1, has been molecularly cloned. Reintroduction of cloned NTS-1 sequences into FE-8 cells resulted in suppression of the neoplastic phenotype in spite of a high ras expression.
Schäfer
R
R
Division of Cancer Research, University of Zürich, Switzerland.
Iyer
J
J
Iten
E
E
Nirkko
A C
AC
Balmer
J
J
Klemenz
R
R
D000818:Animals; D002459:Cell Fusion; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D006801:Humans; D006822:Hybrid Cells; D009374:Neoplasms, Experimental / Q000209:etiology; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors / Q000235:genetics; D009857:Oncogenes; D016366:Open Reading Frames; D010641:Phenotype; D010920:Placenta; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D051381:Rats / Q000196:embryology; D011994:Recombinant Proteins / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D014162:Transfection
D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases