Mutation analysis of the coding sequences of MEK-1 and MEK-2 genes in human lung cancer cell lines.
Recently, constitutively active mutants of MEK (MAP/ERK kinase) were shown to be capable of transforming cells to tumorigenicity suggesting that MEK can function as a dominant oncogene and potentially play a role in human carcinogenesis. Human lung cancer cells exhibit mutations 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 single strand conformation polymorphism analysis and DNA sequencing for alterations 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 acid change) with an allele frequency of 0.5 for each form. These results suggest that mutations in the MEK-1 and MEK-2 gene occur at a very low frequency in human lung cancer.
Bansal
A
A
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Ramirez
R D
RD
Minna
J D
JD
D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics*; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C482128:MAP2K2 protein, human; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases