MUTATION ANALYSIS OF THE CODING SEQUENCES OF MEK-1 AND MEK-2 GENES INHUMAN LUNG-CANCER CELL-LINES

Recently, constitutively active mutants of MEK (MAP/ ERI( kinase) were shown to be capable of transforming cells to tumorigenicity suggestin g that MEK can function as a dominant oncogene and potentially play a role in human carcinogenesis, Human lung cancer cells exhibit mutation s in other components of the MAP kinase signaling pathway such as the Her-2/neu and ras oncogenes. Thus, the coding sequences of both MEK-1 and MEK-2 cDNAs from human lung cancer cell lines were screened by sin gle strand conformation polymorphism analysis and DNA sequencing for a lterations in these two genes. In 37 lung cancer cell lines we found: an allelic variant in MEK-1 cDNA, nt 783 G-->A, (no amino acid change) ; a MEK-2 cDNA change (nt 977 C-->T mutation leading to 298 Pro-->Leu change); a MEK-2 cDNA change nt 537 C-->T (no amino acid change); and a frequent MEK-2 cDNA germline polymorphism nt 744, A-->C (no amino ac id change) with an allele frequency of 0.5 for each form. These result s suggest that mutations in the MEK-1 and MEK-2 gene occur at a very l ow frequency in human lung cancer.