Identification of novel cellular genes transcriptionally suppressed by v-src.
Our aim is to identify cellular genes whose transcriptional suppression by the v-src oncogene contributes directly and specifically to the transformed and tumorigenic phenotype. We used a modified PCR-based subtractive hybridization technique to isolate 9 cDNAs whose abundance in NIH3T3 fibroblasts is decreased 3-15-fold following transformation by the activated oncogene, v-src. Sequence analysis reveals that 3 cDNAs are unlike those in GenBank. The remaining 6 cDNAs are indentical or highly similar to rat helix-destabilizing protein gene (hnRNP A1), mouse CTLA-2 alpha cysteine protease, rat cytochrome c oxidase (COX) VIc subunit, mouse Type I collagen, human gravin and a partial human cDNA (clone A7C09) isolated by random automated sequencing. Northern blot analysis indicates that the basal level of transcripts in untransformed NIH3T3 of all the genes except mouse Type I collagen was at least 10-fold lower than that of HMG Co-A Reductase, which is abundantly transcribed. These data suggest that the down-regulation of some or all of these genes contributes to v-src-induced changes in mitogenic control or cell morphology.
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029.
B J
BJ
Frankfort
I H
IH
Gelman
D016475:3T3 Cells; D054758:A Kinase Anchor Proteins; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D003094:Collagen / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins; D003576:Electron Transport Complex IV / Q000235:genetics; D016391:Genes, src; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D012261:Ribonucleoproteins; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013489:Suppression, Genetic; D013951:Thymus Hormones; D014158:Transcription, Genetic; D014764:Viral Proteins
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; C491161:Akap12 protein, mouse; C102361:Akap12 protein, rat; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D011506:Proteins; D012261:Ribonucleoproteins; D013951:Thymus Hormones; D014764:Viral Proteins; C060035:gp32 protein, Enterobacteria phage T4; C027729:helix-destabilizing proteins; D003094:Collagen; D003576:Electron Transport Complex IV; D003546:Cysteine Endopeptidases; D004265:DNA Helicases