Abstract：
:Kiss-1 has been identified as a putative metastasis suppressor gene in various human malignancies. However, there is little information about its possible role in gastric carcinoma. In this study, we determined whether the Kiss-1 gene negatively regulates MMP-9 expression. cDNA microarray technology was used to identify the genes associated with metastasis by hepatocyte growth factor (HGF) in the gastric cancer cell lines, NUGC-3 and MKN-28. The levels of Kiss-1 RNA and protein were confirmed to be upregulated in HGF-treated gastric cancer cells. HGF induced Kiss-1 and MMP-9 production in a dose-dependent manner. In order to investigate roles of HGF signaling in tumor progression and metastasis, we measured effects of a specific MEK1 inhibitor (PD 098059) and a p38 kinase inhibitor (SB 203580) on HGF-mediated cell proliferation and MMP-9. Pretreatment with PD 098059 reduced MMP-9 and HGF-mediated cell proliferation, but increased Kiss-I expression. In contrast, SB 203580 pretreatment enhanced MMP-9 and cell prolifera-tion, but decreased Kiss-1 expression. Cotreatment of PD098059 and SB203580 increased the p38 phosphorylation stimulated by HGF. These results suggest that the HGF-mediated Kiss-1 overexpression is regulated mainly by the p38 activation and, furthermore, the activation of ERK might affect HGF-mediated Kiss-1 expression indirectly by the regulation of p38 kinase. Consistent with this result, p38 phosphorylation was strongly repressed by the knock-down of Kiss-1. Downregulation of Kiss-1 using Kiss-1 shRNA also increased in vitro cell invasion. In conclusion, Kiss-1 suppresses MMP-9 expression by activating the p38 MAP kinase signaling pathway.
journal_name
Oncol Resjournal_title
Oncology researchauthors
Lee KH,Kim JRdoi
10.3727/096504009789954591subject
Has Abstractpub_date
2009-01-01 00:00:00pages
107-16issue
2-3eissn
0965-0407issn
1555-3906journal_volume
18pub_type
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journal_title：Oncology research
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doi：
更新日期：1995-01-01 00:00:00
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pub_type： 临床试验,杂志文章
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更新日期：1994-01-01 00:00:00
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