| Project/Area Number |
13671291
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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 | Fukui Medical University |
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Principal Investigator |
GOI Takanori Fukui Medical University, Faculty of Medicine, Assistant, 医学部, 助手 (60225638)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Akio Fukui Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10174608)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | PPP2R1B gene / Protein phosphatase / PP2A protein / colorectal cancer / PPP2R1B / PP2A-A蛋白質 / プロテインフォスファターゼ |
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| Research Abstract |
Background : The chromosome region 11q is frequently deleted in colorectal cancers. The PPP2R1B tumor suppressor gene, encoding the β isoform of the A subunit of serine/threonine-specific protein phosphatase 2A (PP2A-Aβ), located at 11q22-23, is inactivated in patients with cancer. The present study determines whether or not PP2A-Aβ is altered in colorectal cancers.
Method : We searched for alterations of the PPP2R1B gene and interactions between PP2A-Aβ and PP2A-C proteins in 50 surgically resected colorectal cancer tissues.
Results : Missense mutations and homozygous deletions of the PPP2R1B gene were found in four of 50 patients (8 %) and in one of 50 patients, respectively, with colorectal cancers. Deletions and/or point mutations within 412-601 amino acid sequences (binding regions of PP2A-C protein) of the PPP2R1B gene derived from colorectal cancer tissues inhibited co-immunoprecipitation of PP2A-Aβ and PP2A-C proteins.
Conclusion : These finding suggest that the PPP2R1B gene functions as a tumor suppressor gene and acts as a molecular switch that becomes active in response to specific upstream signals. Upon activation, the gene alters the activities of specific downstream target proteins for the cell cycle regulations and/or metabolism in some colorectal cancers.
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