RRC ID 12754
Author Saitoh Y, Martínez Bruyn VJ, Uota S, Hasegawa A, Yamamoto N, Imoto I, Inazawa J, Yamaoka S.
Title Overexpression of NF-κB inducing kinase underlies constitutive NF-κB activation in lung cancer cells.
Journal Lung Cancer
Abstract The present study investigates roles for NF-κB inducing kinase (NIK) in constitutive NF-κB activation in lung cancer cells. A wealth of evidence showed that NF-κB is often constitutively activated in human cancer cells, including non-small cell lung cancer tissue specimens and cell lines, which may lead to deregulated apoptosis and enhanced resistance of tumor cells to chemotherapy. However, the mechanisms of NF-κB activation in lung cancer cells remain largely unknown. We report here that NF-κB inducing kinase (NIK) is aberrantly expressed at the pre-translational level in non-small cell lung cancer (NSCLC) cell lines. Depletion of NIK by RNA interference remarkably diminished nuclear NF-κB DNA binding activity and reporter gene expression. NIK depletion induced apoptosis in A549 cells, reduced the matrix metalloproteinase 9 (MMP-9) and survivin mRNA expression and affected efficiency of anchorage-independent H1299 cell growth, suggesting a role for NIK in the manifestation of oncogenic phenotype. These results indicate that NIK plays a key role in constitutive NF-κB activation in NSCLC cells and implicate NIK as a molecular target for lung cancer therapy.
Volume 70(3)
Pages 263-70
Published 2010-12
DOI 10.1016/j.lungcan.2010.03.001
PII S0169-5002(10)00112-1
PMID 20338663
MeSH Apoptosis / genetics Carcinoma, Non-Small-Cell Lung / genetics* Carcinoma, Non-Small-Cell Lung / metabolism Carcinoma, Non-Small-Cell Lung / pathology Cell Growth Processes / genetics Cell Line, Tumor Gene Expression Regulation, Neoplastic Humans Inhibitor of Apoptosis Proteins / genetics Inhibitor of Apoptosis Proteins / metabolism Lung Neoplasms / genetics* Lung Neoplasms / metabolism Lung Neoplasms / pathology Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism NF-kappa B / genetics NF-kappa B / metabolism* Protein Binding / genetics Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism* RNA, Small Interfering / genetics Transcriptional Activation* / genetics Transgenes / genetics
IF 4.599
Times Cited 17
DNA material CS-CDF-CG-PRE (RDB04379)