Detection of differentially expressed genes in mouse lung adenocarcinomas

Increasing evidence suggests that altered gene expression is associated wit h the induction and maintenance of malignancy in various organs including m ouse lung adenocarcinomas. A competitive cDNA library screening (CCLS) was wed to examine gene expression in 4-(methylnitrosamino)-1 (3-pyridyl)-1-but anone- induced lung adenocarcinomas from (C3H/HeJ x A/J])F-1 mice. Comparis ons of RNA expression in lung adenocarcinomas to those of normal surroundin g lung tissue revealed altered expression in 220 clones from more than 50,0 00 clones screened. Fifty clones were selected for quantitative reverse tra nscriptase-polymerase chain reaction (PCR) analysis to verify altered expre ssion. PCR primers were designed based on partial sequence analysis of the clones. Twenty-two clones were found to be differentially expressed in lung adenocarcinomas compared with normal lungs. GenBank database analysis show ed that 14 of the 22 clones were homologous with known genes, whereas 8 clo nes contained novel sequences. Thirteen clones were down regulated In tumor s compared to normal lung tissues, and 9 were overexpressed. The clones und erexpressed or absent include adipocyte p27, carbonic anhydrase III, carbon yl reductase, cytochrome CYP2E1, skelemin, myosin, major urinary protein, a nd contrapsin. Overexpressed clones include Bruton's tyrosin kinase, cyclin D3, poly(A)-binding protein, alpha-fetoprotein, transferrin, and mouse B2 family repetitive sequence. Further examination of biologic implications of the differentially expressed genes in lung adenocarcinomas is necessary to understand their role(s) in mouse lung carcinogenesis.