Using retroviruses as insertional mutagens to identify cellular oncogenes.
Three criteria have been used to identify cellular genes that might play a role in oncogenesis: (i) homology with known viral transforming genes (v-onc's); (ii) activated expression in tumor cells; and (iii) transforming activity in cultured mouse cells. We have been exploring the hypothesis that retroviruses lacking oncogenes activate cellular oncogenes by insertional mutagenesis. Our approach is to locate proviruses within the chromosomal DNA of clonal populations of tumor cells, and to identify activated transcriptions of tumor cells, and to identify activated transcriptional units in flanking cellular DNA. The central findings that have emerged from such studies in our laboratory and others indicate that: (i) insertion of avian leukosis virus (ALV) DNA can activate c-myc, a previously identified cellular homologue of a viral transforming gene, by various arrangements of proviral and c-myc DNA; (ii) most mammary carcinomas in C3H mice carry new mouse mammary tumor virus (MMTV) proviruses within an unidentified 20 kilobase region of the mouse genome that contains at least one activated transcriptional unit; (iii) proviruses of three viruses (ALV), chicken syncytial virus (CSV), and myeloblastosis-associated virus (MAV) are present in the c-myc locus in avian B cell lymphomas, suggesting that the same gene is activated during induction of a single type of tumor by different viruses; and (iv) MAV-induced nephroblastomas do not contain proviral insertions near c-myc, implying that the same virus may affect different genes in different types of tumor.
D000818:Animals; D002472:Cell Transformation, Viral; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005809:Genes, Regulator; D051379:Mice; D009154:Mutation; D009857:Oncogenes; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics*
D004273:DNA, Neoplasm; D004279:DNA, Viral