| RRC ID |
12754
|
| 著者 |
Saitoh Y, Martínez Bruyn VJ, Uota S, Hasegawa A, Yamamoto N, Imoto I, Inazawa J, Yamaoka S.
|
| タイトル |
Overexpression of NF-κB inducing kinase underlies constitutive NF-κB activation in lung cancer cells.
|
| ジャーナル |
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.
|
| 巻・号 |
70(3)
|
| ページ |
263-70
|
| 公開日 |
2010-12-1
|
| 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
Survivin
Transcriptional Activation* / genetics
Transgenes / genetics
|
| IF |
4.702
|
| 引用数 |
22
|
|
WOS 分野
|
RESPIRATORY SYSTEM
ONCOLOGY
|
| リソース情報 |
| 遺伝子材料 |
CS-CDF-CG-PRE (RDB04379) |
