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Mutational activation of the MAP3K8 protooncogene in lung cancer.

Authors
Clark-AM; Reynolds-SH; Anderson-M; Wiest-JS
Source
Genes Chromosomes Cancer 2004 Oct; 41(2):99-108
NIOSHTIC No.
20025474
Abstract
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.
Keywords
Lung-cancer; Cancer; Pulmonary-system-disorders; Respiratory-system-disorders; Laboratory-animals; Animals; Animal-studies; Humans; Tumors; Carcinomas; Tumorigenesis
Contact
Jonathon S. Weist, National Cancer Institute, 31 Center Drive, Building 31A/Rm 3A11, Bethesda, MD 20892
CODEN
GCCAES
Publication Date
20041001
Document Type
Journal Article
Email Address
wiestj@mail.nih.gov
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1045-2257
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Genes, Chromosomes and Cancer
State
WV; OH; MD
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