Hormonal regulation of the Rous sarcoma virus src gene via a heterologous promoter defines a threshold dose for cellular transformation.
We have derived rat cell lines producing different and regulatable amounts of pp60v-src by introducing the src gene of Rous sarcoma virus (RSV) under the control of the glucocorticoid-responsive transcriptional promoter from the mouse mammary tumor virus (MMTV). We find that the cellular phenotype is strictly dependent upon the dose of pp60v-src with a distinct threshold for changes indicative of neoplastic potential. Cells with low constitutive levels of pp60v-src are not phenotypically distinguishable from cells without v-src, but as little as a 4-fold increment in pp60v-src produces morphological transformation and anchorage-independent growth. These properties of the transformed state are achieved at levels of pp60v-src far below levels found in an RSV-transformed cell line, without detectable increase in phosphorylation of the major cellular target for tyrosine phosphorylation.
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000201:enzymology / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004262:DNA Restriction Enzymes; D003907:Dexamethasone / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects*; D005814:Genes, Viral / Q000187:drug effects*; D005822:Genetic Vectors; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D015688:Oncogene Protein pp60(v-src); D010766:Phosphorylation; D010957:Plasmids; D011494:Protein Kinases / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
D014764:Viral Proteins; D003907:Dexamethasone; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); D004262:DNA Restriction Enzymes