Mutational activation of the MAP3K8 protooncogene in lung cancer. Genes Chromosomes Cancer 2004 Oct;41(2):99-108
Date
08/03/2004Pubmed ID
15287022Pubmed Central ID
PMC3459321DOI
10.1002/gcc.20069Scopus ID
2-s2.0-4143062439 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
The MAP3K8 protooncogene (Cot/Tpl-2) activates the MAP kinase, SAP kinase, and NF-kappaB signaling pathways. MAP3K8 mutations occur in the rat homologue, but activating mutations have yet to be identified in primary human tumors. We have identified MAP3K8 as a transforming gene from a human lung adenocarcinoma and characterized a 3' end mutation in the cDNA. In addition, we confirmed that the mutation occurs in the original lung tumor, and we screened a series of lung cancer cell lines to determine whether the MAP3K8 mutation is a common occurrence in lung tumorigenesis. The oncogene was isolated and identified with the NIH3T3 nude mouse tumorigenicity assay and cDNA library screening. The gene was analyzed by polymerase chain reaction (PCR), single-strand conformational polymorphism (SSCP), and 3'RACE for mutations. The mutation was localized to MAP3K8 exon 8 and confirmed in the primary tumor DNA. Both wild-type and mutant MAP3K8 cDNAs transformed NIH3T3 cells, but the transforming activity of the mutant was much greater than that of the wild type. PCR-SSCP screening of cell line cDNAs identified one silent polymorphism in cell line SK-LU-1. Although we were unable to find additional activating mutations, these data support a role for MAP3K8 activity in cellular transformation, but suggest that mutational activation of the gene is a rare event in lung cancer.
Author List
Clark AM, Reynolds SH, Anderson M, Wiest JSMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAmino Acid Sequence
Animals
Base Sequence
DNA Primers
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
MAP Kinase Kinase Kinases
Mice
Mice, Nude
Molecular Sequence Data
Mutation
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Proto-Oncogene Proteins
Rats
Sequence Alignment
Sequence Homology, Amino Acid
Thyroid Neoplasms
Transplantation, Heterologous
