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KMID : 0620920060380010027
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Experimental & Molecular Medicine
2006 Volume.38 No. 1 p.27 ~ p.35
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Regulation of hepatocyte growth factor-mediated urokinase plasminogen activator secretion by MEK/ERK activation in human stomach cancer cell lines
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Lee Kyung-Hee
Choi Eun-Young
Kim Min-Kyoung
Hyun Myung-Soo
Jang Byung-Ik
Kim Tae-Nyeun
Kim Sang-Woon
Song Sun-Kyo
Kim Jung-Hye
Kim Jae-Ryong
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Abstract
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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.
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KEYWORD
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hepatocyte growth factor, mitogen-activated protein kinases, neoplasm metastasis, urinary plasminogen activator
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