title: The ribonucleotide reductase R2 gene is a non-transcribed target of c-Myc-induced genomic instability.
abstract: The c-Myc oncoprotein is highly expressed in malignant cells of many cell types, but the mechanism by which it contributes to the transformation process is not fully understood. Here, we show for the first time that constitutive or activated overexpression of the c-myc gene in cultured mouse B lymphocytes is followed by chromosomal and extrachromosomal amplification as well as rearrangement of the ribonucleotide reductase R2 gene locus. Electron micrographs and fluorescent in situ hybridization (FISH) demonstrate the c-Myc-dependent generation of extrachromosomal elements, some of which contain R2 sequences. However, unlike other genes that have been shown to be targets of c-Myc-dependent genomic instability, amplification of the R2 gene is not associated with alterations in R2 mRNA or protein expression. These data suggest that c-Myc-dependent genomic instability involves a greater number of genes than previously anticipated, but not all of the genes that are amplified in this system are transcriptionally upregulated.
authors.affiliation: Manitoba Institute of Cell Biology and the Manitoba Cancer Treatment and Research Foundation, Winnipeg, Canada.
authors.forename: T I
authors.initials: TI
authors.lastname: Kuschak
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: E
authors.initials: E
authors.lastname: McMillan-Ward
authors.forename: S
authors.initials: S
authors.lastname: Israels
authors.forename: D W
authors.initials: DW
authors.lastname: Henderson
authors.forename: J F
authors.initials: JF
authors.lastname: Mushinski
authors.forename: J A
authors.initials: JA
authors.lastname: Wright
authors.forename: S
authors.initials: S
authors.lastname: Mai
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D015139:Blotting, Southern; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008854:Microscopy, Electron; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012264:Ribonucleotide Reductases / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012264:Ribonucleotide Reductases