Regulation of hepatocyte growth factor-mediated urokinase plasminogen activator secretion by MEK/ERK activation in human stomach cancer cell lines.
- Author:
Kyung Hee LEE
1
;
Eun Young CHOI
;
Min Kyoung KIM
;
Myung Soo HYUN
;
Byung Ik JANG
;
Tae Nyeun KIM
;
Sang Woon KIM
;
Sun Kyo SONG
;
Jung Hye KIM
;
Jae Ryong KIM
Author Information
1. Department of Hemato-Oncology, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
hepatocyte growth factor;
mitogen-activated protein kinases;
neoplasm metastasis;
urinary plasminogen activator
- MeSH:
Cell Line, Tumor;
Cell Proliferation/drug effects;
Culture Media, Serum-Free;
Dose-Response Relationship, Drug;
Enzyme Activation/drug effects;
Enzyme Inhibitors/pharmacology;
Extracellular Signal-Regulated MAP Kinases/metabolism;
Flavonoids/pharmacology;
Hepatocyte Growth Factor/*pharmacology;
Humans;
Imidazoles/pharmacology;
Kinetics;
MAP Kinase Kinase 1/metabolism;
Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism;
Neoplasm Metastasis;
Phosphorylation/drug effects;
Pyridines/pharmacology;
Research Support, Non-U.S. Gov't;
Stomach Neoplasms/*enzymology/*pathology;
Urinary Plasminogen Activator/*secretion;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:Experimental & Molecular Medicine
2006;38(1):27-35
- CountryRepublic of Korea
- Language:English
-
Abstract:
The regulatory mechanisms for the proliferation and the particular invasive phenotypes of stomach cancers are not still fully understood. Up-regulations of hepatocytes growth factor (HGF), its receptor (c-Met), and urokinase-type plasminogen activator (uPA) are correlated with the development and metastasis of cancers. In order to investigate roles of HGF/c-Met signaling in tumor progression and metastasis in stomach cancers, we determined effects of a specific MEK1 inhibitor (PD098059) and a p38 kinase inhibitor (SB203580) on HGF-mediated cell proliferation and uPA expression in stomach cancer cell lines (NUGC-3 and MKN-28). HGF treatment induced the phosphorylations of ERK and p38 kinase in time- and dose- dependent manners. Pre-treatment with PD098059 reduced HGF-mediated cell proliferation and uPA secretion. In contrast, SB203580 pre-treatment enhanced cell proliferation and uPA secretion due to induction of ERK phosphorylation. Stable expression of dominant negative-MEK1 in NUGC-3 cells showed a decrease in HGF-mediated uPA secretion. These results suggest that interaction of a MEK/ERK and a p38 kinase might play an important role in proliferation and invasiveness of stomach cancer cells.
