| Project/Area Number |
17591414
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
YAMAGUCHI Kouji Kyushu University, Faculty of Medical Sciences, Associate Professor, 大学院医学研究院, 助教授 (50191226)
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| Co-Investigator(Kenkyū-buntansha) |
KATANO Mitsuo Kyushu University, Faculty of Medical Sciences, Professor, 大学院医学研究院, 教授 (10145203)
NOMURA Masatoshi Kyushu University, Faculty of Medical Sciences, Research Associate, 大学病院, 助手 (30315080)
NOMURA Masafumi Kyushu University, Faculty of Medical Sciences, Associate Professor, 大学院医学研究院, 助教授 (30372741)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | IL1-β / pancreatic cancer / Hedgehog / NFkB / inflammation / obstructive pancreat it is / Sonic Hedgehog / invasion |
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| Research Abstract |
It has been reported that Hedgehog (HH) signal activation of ligand (Shh) dependence participates in pancreas carcinogenesis and development, but Shh is not clarified about mechanism developing excessively in any cancers including pancreatic cancer. In this theme, we analyzed the correlation between activity of nuclear factor-KB (NF-κB) and expression level of Shh in pancreatic cancer, because NF-κB is usually activated by obstructive pancreatitis caused by pancreatic cancer. We found a positive correlation between NF-κB p65 and Shh expression in surgically resected pancreas specimens, including specimens of chronic pancreatitis and pancreatic adenocarcinoma. Suppression of NF-κB by PDTC, decoy ODN or dominant-negativeNF-κB suppressed constitutive expression of Shh mRNA in pancreatic cancer cells. Vice versa, three inflammatory stimuli including IL1-β, TNF-a and LPS induced overexpression of Shh, resulting in activation of the Hh pathway, consistent with that blockade of NF-κB suppressed overexpression of Shh induced by these stimuli. Importantly, NF-KB-induced HH signal activation enhanced cell proliferation in pancreatic cancer cells. In addition, inhibition of the Hh pathway as well as NF-κB suppressed the enhanced cell invasion. Our data suggest that NF-κB activation is one of the mechanisms controling Shh overexpression in pancreatic cancer and that proliferation and invasion of pancreatic cancer cells is accelerated by NF-κB activation in part through HH signaling pathway.
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