Inhibition of histone deacetylase activity down-regulates urokinase plasminogen activator and matrix metalloproteinase-9 expression in gastric cancer

Title
Inhibition of histone deacetylase activity down-regulates urokinase plasminogen activator and matrix metalloproteinase-9 expression in gastric cancer
Author(s)
이경희최은영[최은영]김민경김경옥장병익김세원김상운송선교김재룡
Keywords
HEPATOCYTE GROWTH-FACTOR; PROGNOSIS; THERAPY; CARCINOGENESIS; CARCINOMAS; APICIDIN; INVASION; PROTEIN; SYSTEM; TUMOR
Issue Date
201003
Publisher
SPRINGER
Citation
MOLECULAR AND CELLULAR BIOCHEMISTRY, v.343, no.1-2, pp.163 - 171
Abstract
Histone acetylation and deacetylaion play important roles in chromatin remodeling and gene expression. An imbalance of these reactions leads to aberrant behavior of the cells in the cell cycle, which in turn contributes to carcinogenesis. Histone deacetylase (HDAC) inhibitors have been shown to have anti-tumor effects in clinical trials. However, the exact mechanisms by which HDAC inhibitors exert anti-tumor effects and modulate gene expression are not completely understood, and remain a subject of intense investigation. In the current study, we determined whether HDACs regulate urokinase plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and tumor invasion. Using cDNA microarray analysis, we found that hepatocyte growth factor (HGF) induced HDAC5 expression in gastric cancer cell lines, NUGC-3 and MKN-28. TSA, a HDAC inhibitor, decreased HGF-induced HADC-5 expression and also repressed uPA and MMP-9 expression. TSA inhibited cell proliferation in both cell lines. In vitro Matrigel invasion assays showed that the HDAC inhibitor decreased cancer cell invasion. Furthermore, GO6976, a PKC inhibitor, significantly inhibited not only HGF-induced HDAC5 expression but also cell invasion. These results demonstrated that HDACs regulate HGF-induced uPA and MMP-9 expression through a PKC-dependent signal pathway in gastric cancer cells. Our data probably suggest that such activities serve as anti-tumor mechanisms of the HDAC inhibitor.
URI
http://hdl.handle.net/YU.REPOSITORY/22791http://dx.doi.org/10.1007/s11010-010-0510-x
ISSN
0300-8177
Appears in Collections:
의과대학 > 내과학교실 > Articles
의과대학 > 성형외과학교실 > Articles
의과대학 > 생화학.분자생물학교실 > Articles
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