2007 Fiscal Year Final Research Report Summary
Elucidation of a potential role of poly-ADP-ribosylation in the carcinogenesis or development of human colorectal carcinoma and its application for the diagnosis or trteatment of human colorectal carcinoma
| Project/Area Number |
18591456
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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 | Chiba University |
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Principal Investigator |
NABEYA Yoshihiro Chiba University, Dept. of Frontier Surgery, Associate Professor (40322028)
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| Co-Investigator(Kenkyū-buntansha) |
NODA Masatoshi Chiba University, Dept. of Molecular Infectiology, Professor (60164703)
MORINAGA Naoko Chiba University, Dept. of Molecular Infectiology, Associate Professor (20092108)
SHIMIZU Ken Chiba University, Dept. of Molecular Infectiology, Associate Professor (70312840)
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| Project Period (FY) |
2006 – 2007
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| Keywords | colorectal cancer / adenosine 5' -diphosphate (ADP)-ribosylation / protein / surgery |
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| Research Abstract |
Objective: Poly-adenosine 5'-diphosphate (ADP)-ribosylation, catalyzed by poly (ADP-ribose) polymerase (PARP), transfers poly-ADP-ribose moieties from nicotinamide adenine dinucleotide (NAD) to an acceptor protein. It is an important post-translational modification of nuclear proteins and is involved in various biological processes including malignant transformation. Thus, the aim of this study was to evaluate poly-ADP-ribosylation and to compare the expression of PARP in human colorectal carcinomas (CRCs) and adjacent non-tumorous mucosae.
Methods: Tumorous and adjacent non-tumorous tissues were obtained from surgically removed colorectums of 15 patients with CRC, and then were homogenized into cytosolic and membranous fractions. Each homogenate was assayed for ADP-ribosylation with [adenylate-^<32> P] -NAD. The radiolabeled proteins were separated by electrophoresis and autoradiography. The ADP-ribosylated protein was partially purified by anion exchange column chromatography, and analyzed by time-of-flight mass spectrometry (TOF-MS) and immunoprecipitation. Expression of PARP was also evaluated by Western blotting.
Results: Several proteins were ADP-ribosylated in human CRC tissues. Notably, the remarkable radiolabeling of a 113-kDa protein was found in the cytosolic fractions from CRCs, and greater than that in adjacent non-tumorous mucosae in 13/15 subjects (87 %). Inhibition assays revealed that the reaction was enzymatic poly-ADP-ribosylation. By TOF-MS and immunoprecipitation, the 113-kDa protein was found to be tumor rejection antigen, glycoprotein (gp) 96. The expression of PARP was significantly greater in CRCs than in adjacent non-tumorous mucosae, while the expression of gp96 in CRCs and normal mucosae was identical.
Conclusion: Poly-ADP-ribosylation of gp 96 and PARP expression were increased in human CRCs compared with those in adjacent non-tumorous mucosae, and it may be implicated in the carcinogenesis or development of human CRC.
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[Journal Article] Enhanced poly- (adenosine 5'-diphosphate) -ribosylation of glycoprotein 96 in human colorectal carcinoma2006
Author(s)
Nabeya, Y., Inoue, M., Yahiro, K, Morinaga, N., Sakamoto, A., Noda, M. and Ochiai, T.
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Journal Title
Abstract DVD of 20th World Congress of International Society for Digestive Surgery 305
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Enhanced poly-(adenosine 5'-diphosphate)-ribosylation of glycoprotein 96 in human colorectal carcinoma2006
Author(s)
Nabeya, Y., Inoue, M., Yahiro, K., Morinaga, N., Sakamoto, A., Noda, M. and Ochiai, T.
Organizer
20th World Congress of International Society for Digestive Surgery
Place of Presentation
Rome, Italy
Year and Date
2006-11-30
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Identification of a protein which can receive poly-(adenosine 5'-diphosphate)-ribosylation in human colorectal carcinoma2006
Author(s)
Inoue, M., Nabeya, Y., Yahiro, K, Akai, T., Miyazaki, S., Sakamoto, A., Noda, M. and Ochiai, T.
Organizer
68th Annual Meeting of Japan Surgical Association
Place of Presentation
Hiroshima
Year and Date
2006-11-09
Description
「研究成果報告書概要(欧文)」より
