DETECTION OF DIFFERENTIALLY EXPRESSED GENES IN METHYLNITROSOUREA-INDUCED RAT MAMMARY ADENOCARCINOMAS

In this study, altered gene expression in five methylnitrosourea (MNU) -induced rat mammary adenocarcinomas was investigated using a newly de veloped competitive cDNA library screening assay. In order to detect t he differentially expressed cDNA transcripts, three cDNA libraries (ra t mammary, rat liver, and rat kidney) with over 18,000 clones were dif ferentially screened with competing normal and neoplastic mammary cDNA probes. Ninety-eight clones indicated by competitive hybridization to be differentially expressed in tumors were verified by dot-blot hybri dization analysis. Of these clones, 45 were found to be overexpressed while 53 were underexpressed in tumors. Forty-five of the confirmed cl ones were further analyzed by single-pass cDNA sequence determination. Four clones showed homology with cytochrome oxidase subunit I, polyom a virus PTA noncoding region, cytoplasmic beta-actin, and mouse secret ory protein containing thrombospondin motifs. Further investigation in to the potential roles of these identified genes should contribute sig nificantly to our understanding of the molecular mechanism(s) of rat m ammary tumorigenesis. (C) 1998 Wiley-Liss, Inc.