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‐β (TGF‐β)–elicited signals in the pathogenesis of this most common cancer. In the present study, we investigated whether another downstream mediator, human TGF‐β‐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. Int. J. Cancer 75:559–563, 1998. © 1998 Wiley‐Liss, Inc.

[1]  B. Vogelstein,et al.  Nomenclature: Vertebrate Mediators of TGFβ Family Signals , 1996, Cell.

[2]  K. Cooney,et al.  Identification and characterization of proximal 6q deletions in prostate cancer. , 1996, Cancer research.

[3]  T. Mitsudomi,et al.  Somatic in vivo alterations of the DPC4 gene at 18q21 in human lung cancers. , 1996, Cancer research.

[4]  K. Irie,et al.  TAB1: An Activator of the TAK1 MAPKKK in TGF-β Signal Transduction , 1996, Science.

[5]  A. Marchetti,et al.  Multiple regions of chromosome 6q affected by loss of heterozygosity in primary human breast carcinomas. , 1996, British Journal of Cancer.

[6]  K. Irie,et al.  Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction , 1995, Science.

[7]  D. Haber,et al.  WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis. , 1995, The EMBO journal.

[8]  M. Santibanez-Koref,et al.  Allelic imbalance of chromosome 6q in ovarian tumours. , 1995, British Journal of Cancer.

[9]  R. Ueda,et al.  Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. , 1995, Oncogene.

[10]  M. Santibanez-Koref,et al.  Proximal 6q, a region showing allele loss in primary breast cancer. , 1995, British Journal of Cancer.

[11]  J. Siegfried,et al.  Cytogenetic analysis of 63 non‐small cell lung carcinomas: Recurrent chromosome alterations amid frequent and widespread genomic upheaval , 1994, Genes, chromosomes & cancer.

[12]  T. Taniguchi,et al.  Accelerated exon skipping of IRF-1 mRNA in human myelodysplasia/leukemia; a possible mechanism of tumor suppressor inactivation. , 1994, Oncogene.

[13]  F. Mitelman,et al.  Karyotypic characterization of bronchial large cell carcinomas , 1994, International journal of cancer.

[14]  M. Santibanez-Koref,et al.  Deletion of a common region on the long arm of chromosome 6 in acute lymphoblastic leukaemia , 1994, Genes, chromosomes & cancer.

[15]  C. Croce,et al.  Suppression of tumorigenicity of breast cancer cells by microcell-mediated chromosome transfer: studies on chromosomes 6 and 11. , 1994, Cancer research.

[16]  R. Ueda,et al.  Aberrant upregulation of a novel integrin alpha subunit gene at 3p21.3 in small cell lung cancer. , 1994, Oncogene.

[17]  D. Haber,et al.  WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant. , 1993, Science.

[18]  S. Jhanwar,et al.  Recurrent deletions of specific chromosomal sites in 1p, 3p, 6q, and 9p in human malignant mesothelioma. , 1993, Cancer research.

[19]  R. Ueda,et al.  Glutathione S-transferase pi levels in a panel of lung cancer cell lines and its relation to chemo-radiosensitivity. , 1993, Japanese journal of clinical oncology.

[20]  M. Sporn,et al.  Physiological Actions and Clinical Applications of Transforming Growth Factor-β (TGF-β) , 1993 .

[21]  K. Tajima,et al.  Prediction of future cancer mortality in Japan. , 1992, Japanese journal of clinical oncology.

[22]  K. Offit,et al.  Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma. , 1992, Blood.

[23]  J. Trent,et al.  Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma. , 1991, Cancer research.

[24]  J M Trent,et al.  Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6. , 1990, Science.

[25]  R. Ueda,et al.  Two novel cell surface antigens on small cell lung carcinoma defined by mouse monoclonal antibodies NE-25 and PE-35. , 1986, Cancer research.