title: c-Myc dependent initiation of genomic instability during neoplastic transformation.
abstract: The dihydrofolate reductase (DHFR) gene is a target of c-Myc in genomic instability. The induced overexpression of c-Myc in cell lines is followed by the amplification and rearrangement of the DHFR gene. Furthermore, the constitutive upregulation of c-Myc protein coincides with genomic instability of the DHFR gene in lymphoid, non-lymphoid and in tumor lines. The amplification of the DHFR gene is locus-specific and independent of species origins. We have now addressed the question whether inducible deregulation of c-Myc is followed by DHFR gene amplification in vivo. We show that the DHFR gene is a target of c-Myc-dependent neoplasia in vivo and propose a role for genomic instability during the initiation of neoplastic transformation.
authors.affiliation: Manitoba Institute of Cell Biology, Winnipeg, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: A
authors.initials: A
authors.lastname: Jalava
authors.forename: S
authors.initials: S
authors.lastname: Mai
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D005784:Gene Amplification; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D010954:Plasmacytoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013729:Terpenes / Q000633:toxicity; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D002273:Carcinogens; D016271:Proto-Oncogene Proteins c-myc; D013729:Terpenes; C009042:pristane; D013762:Tetrahydrofolate Dehydrogenase