Differential gene expression in chemically induced mouse lung adenomas. Neoplasia 2003;5(1):41-52
Date
03/28/2003Pubmed ID
12659669Pubmed Central ID
PMC1502122DOI
10.1016/s1476-5586(03)80016-7Scopus ID
2-s2.0-0037252353 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
Because of similarities in histopathology and tumor progression stages between mouse and human lung adenocarcinomas, the mouse lung tumor model with lung adenomas as the endpoint has been used extensively to evaluate the efficacy of putative lung cancer chemopreventive agents. In this study, a competitive cDNA library screening (CCLS) was employed to determine changes in the expression of mRNA in chemically induced lung adenomas compared with paired normal lung tissues. A total of 2555 clones having altered expression in tumors were observed following competitive hybridization between normal lung and lung adenomas after primary screening of over 160,000 clones from a mouse lung cDNA library. Among the 755 clones confirmed by dot blot hybridization, 240 clones were underexpressed, whereas 515 clones were overexpressed in tumors. Sixty-five clones with the most frequently altered expression in six individual tumors were confirmed by semiquantitative RT-PCR. When examining the 58 known genes, 39 clones had increased expression and 19 had decreased expression, whereas the 7 novel genes showed overexpression. A high percentage (>60%) of overexpressed or underexpressed genes was observed in at least two or three of the lesions. Reproducibly overexpressed genes included ERK-1, JAK-1, surfactant proteins A, B, and C, NFAT1, alpha-1 protease inhibitor, helix-loop-helix ubiquitous kinase (CHUK), alpha-adaptin, alpha-1 PI2, thioether S-methyltransferase, and CYP2C40. Reproducibly underexpressed genes included paroxanase, ALDH II, CC10, von Ebner salivary gland protein, and alpha- and beta-globin. In addition, CCLS identified several novel genes or genes not previously associated with lung carcinogenesis, including a hypothetical protein (FLJ11240) and a guanine nucleotide exchange factor homologue. This study shows the efficacy of this methodology for identifying genes with altered expression. These genes may prove to be helpful in our understanding of the genetic basis of lung carcinogenesis and in developing biomarkers for lung cancer chemoprevention studies in mice.
Author List
Yao R, Wang Y, Lubet RA, You MMESH terms used to index this publication - Major topics in bold
AdenomaAmino Acid Sequence
Animals
Base Sequence
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Library
Humans
Lung
Lung Neoplasms
Methylnitrosourea
Mice
Mice, Inbred A
Molecular Sequence Data
Neoplasms, Experimental
RNA, Messenger
RNA, Neoplasm
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
