The impact of Bcl-xL upregulation in the development of Kras-mutated pancreatic neoplasia
Project/Area Number |
25860534
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Gastroenterology
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Research Institution | Osaka University |
Principal Investigator |
SHIGEKAWA Minoru 大阪大学, 医学部附属病院, 特任助教(常勤) (00625436)
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Research Collaborator |
IKEZAWA Kenji
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Project Period (FY) |
2013-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 膵癌 / 細胞死 / PanINs / Bcl-xL / アポトーシス |
Outline of Final Research Achievements |
KrasLSL-G12D/+ Pdx1Cre (P-KrasG12D) mice showed PanINs in 2 months and developed PDAC in a year. Immunohistochemistry revealed that Bcl-xL was overexpressed in not only PDAC but also PanINs. Kras knockdown downregulated Bcl-xL expression in Kras-mutated cells (PANC1 and MIA PaCa2) but not in wild-type cells (BxPC3). MEK inhibitors decreased expression levels of Bcl-xL as well as phosphorylated ERK in Kras-mutated cells. Kras mutation induces overexpression of Bcl-xL through MEK-ERK pathway. While P-KrasG12D mice developed PanINs, mainly low-grade, with no PDAC at 4 months, all littermate Bcl-xL Tg/ P-KrasG12D mice developed PDAC at 4 months. The median survival of Bcl-xL Tg/P-KrasG12D mice was 7.6 months, while all P-KrasG12D mice lived in more than one year. Bcl-xL overexpression in Kras-mutated cells accelerated carcinogenesis of PDAC, leading to poor prognosis. Targeted therapy on Bcl-xL may be effective not only as an anti-cancer therapy but also as a preventive therapy for PDAC.
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Report
(3 results)
Research Products
(8 results)
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[Presentation] 膵癌の発生・進展におけるBcl-xLの意義2014
Author(s)
池澤 賢治, 重川 稔, 岩橋 潔, 川口 司, 清水 聡, 名和 誉敏, 疋田 隼人, 阪森 亮太郎, 宮城 琢也, 巽 智秀, 竹原 徹郎
Organizer
第100回 日本消化器病学会総会
Place of Presentation
東京国際フォーラム
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