Molecular cloning of human TAK1 and its mutational analysis in human lung cancer.

In previous reports, we described that DPC4/Smad4 and Smad2 are mutated in a fraction of human lung cancers and suggested possible roles of the downstream mediators of transforming growth factor-beta (TGF-beta)-elicited signals in the pathogenesis of this most common cancer. In the present study, we investigated whether another downstream mediator, human TGF-beta-activated kinase 1 (hTAK1), also is altered in lung cancer. For this purpose, the hTAK1 gene was cloned with the aid of an expression sequence tag database search and cDNA library screening, and hTAK1 was found to be expressed ubiquitously in 2 distinct isoforms regulated in a tissue-specific manner in fetal and adult normal tissues. Interestingly, hTAK1 was assigned to the chromosome region 6q14-21, which is deleted frequently in various human malignancies, including lung cancer. Despite our extensive search for alterations in 39 lung cancer specimens as well as in 16 lung cancer cell lines, somatic mutations of hTAK1 were not identified, indicating that hTAK1 itself is not a frequent target for genetic alterations in lung cancer.