| RRC ID |
6531
|
| 著者 |
Nakamura Y, Matsubara D, Goto A, Ota S, Sachiko O, Ishikawa S, Aburatani H, Miyazawa K, Fukayama M, Niki T.
|
| タイトル |
Constitutive activation of c-Met is correlated with c-Met overexpression and dependent on cell-matrix adhesion in lung adenocarcinoma cell lines.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
In this study we explored the mechanisms of constitutive activation of c-Met in lung adenocarcinoma cell lines. First, we examined levels of c-Met and phospho-c-Met (Y1234/Y1235) in a panel of lung adenocarcinoma cell lines by Western blot analysis. c-Met expression was found in 12 of 14 cell lines and an overall correlation between the expressions of c-Met and phospho-c-Met was noted. c-Met was constitutively activated particularly at high levels in five cell lines (PC3, LC-2/ad, L27, H1648, and H2009). c-Met amplification was identified in L27 and H1648 by single nucleotide polymorphism array analysis, but no mutations were identified in the Sema domain or in any part of the cytoplasmic domain of c-Met. Experiments with neutralizing anti-hepatocyte growth factor (HGF) antibody, scatter assay using Madin-Darby canine kidney cells, and Western blotting on conditioned media of the cell lines revealed that the constitutive phosphorylation of c-Met was largely ligand-independent. The inhibition of cell-matrix adhesion induced the dephosphorylation of c-Met in the five cell lines tested. This was accompanied by downregulation of c-Met in three of the five cell lines. In contrast, the inhibition of cell-cell adhesion by neutralizing E-cadherin antibody had a minimal effect on the expression and phosphorylation of c-Met. These results reveal three features of the constitutive activation of c-Met in our panel of lung adenocarcinoma cell lines: (i) it correlates with c-Met overexpression, either with or without gene amplification; (ii) it is largely ligand-independent; and (iii) it depends on cell-matrix adhesion.
|
| 巻・号 |
99(1)
|
| ページ |
14-22
|
| 公開日 |
2008-1-1
|
| DOI |
10.1111/j.1349-7006.2007.00640.x
|
| PII |
CAS640
|
| PMID |
17953713
|
| MeSH |
Acetylcysteine / analogs & derivatives
Acetylcysteine / pharmacology
Adenocarcinoma / enzymology*
Adenocarcinoma / genetics
Adenocarcinoma / pathology
Animals
Antibodies / immunology
Antibodies / pharmacology
Blotting, Western
Cadherins / antagonists & inhibitors
Cadherins / immunology
Cell Adhesion / physiology
Cell Line, Tumor
Culture Media, Conditioned
DNA, Neoplasm / genetics
Dogs
Down-Regulation / drug effects
Extracellular Matrix / metabolism
Extracellular Matrix / pathology
Hepatocyte Growth Factor / antagonists & inhibitors
Hepatocyte Growth Factor / immunology
Hepatocyte Growth Factor / pharmacology
Humans
Lung Neoplasms / enzymology*
Lung Neoplasms / genetics
Lung Neoplasms / pathology
Oligonucleotide Array Sequence Analysis
Phosphorylation
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-met / biosynthesis
Proto-Oncogene Proteins c-met / genetics
Proto-Oncogene Proteins c-met / metabolism*
Tyrosine / metabolism
|
| IF |
4.966
|
| 引用数 |
35
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HLC-1(RCB0083)
LC-2/ad(RCB0440)
RERF-LC-KJ(RCB1313) |
