2004 Fiscal Year Final Research Report Summary
Detection of dormancy-regulating factors and the related proteins in the proliferation and progression of human gastrointestinal carcinomas
| Project/Area Number |
14370069
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | National University Corporation Tottori University |
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Principal Investigator |
ITO Hisao National University Corporation Tottori University, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (60127610)
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| Co-Investigator(Kenkyū-buntansha) |
MORIYAMA Masatsugu OITA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (90239707)
SHOMORI Kohei National University Corporation Tottori University, FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (60314572)
OSAKI Mitsuhiko National University Corporation Tottori University, FACULTY OF MEDICINE, RESEARCH ASSOCIATE, 医学部, 助手 (40325006)
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| Project Period (FY) |
2002 – 2004
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| Keywords | human gastrointestinal carcinoma / cell cycle / apoptosis / dormancy / RUNX3 / ARPP / COX-2 / FAS |
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| Research Abstract |
1.in vivo analysis
(1)Gastric adenomas are considered to be in dormancy. Comparing with the intramucosal gastric carcinomas, the adenomas showed significantly higher apoptotic index (AI) and lower proliferative activity, which might correlated with intratumoral microvessel density(IMVD) and the expression of thymidine phosphorylase、cyclo-oxygenase(COX)-2、and P53.
(2)RUNX3, a possible tumor suppressor gene, was demonstrated to express in gastric chief cells and G ells, as well as superficial cells of esophageal mucosa and lung alveolar cells, in contrast to obvious lower expression in esophageal, gastric, oral and bronchial carcinomas, in the both operative specimens and cultured cell lines.
(3)A newly confirmed ARPP gene showed to express in the muscle including cardiac muscle and the expression was decreased by denervation.
(4)Human oral, esophageal, gastric, bronchial carcinomas and MFH showed immunohistochemical expression of COX-2, which correlated with IMVD and AI, as well as Skp2 expression.
(5)Fhit expression was correlated with Mlh1, but not P53 expression and early events of carcinogenesis in the gastric, colonic and gall bladder carcinomas.
2.in vitro analysis
(1)RUNX3 gene transfection resulted in cell cycle arrest, but not apoptosis in the human gastric carcinoma cell lines.
(2)COX-2 selective inhibitor caused suppression of cell proliferation and cell cycle arrest, but not apoptosis in the esophageal and gastric carcinoma cell lines.
(3)Signal transduction of Fas-induced apoptosis was conducted via mitochondrial pathway, which was affected by PI3K-Akt activation. PI3K-Akt inhibitor enhanced tumor cell apoptosis.
3.Others
(1)Specific antibodies for ARPP and RUNX3 and RUNX3 expression vector were generated. ARPP knock-out mouse was successfully produced.
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