Elucidation of the mechanism of anticancer activity of the cancer suppressor gene INPP4B
Project/Area Number |
18K06623
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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Research Institution | Akita University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | INPP4B / がん抑制遺伝子 / PTEN / ホスホイノシタイド |
Outline of Final Research Achievements |
We generated genetically engineered mice that express the human INPP4B gene in a cell- and tissue-specific manner and crossed them with liver-specific Pten gene-deficient mice, which are carcinogenesis model mice, to create mice that compensatory express INPP4B in a cell-specific manner in liver cells lacking the Pten gene. The results showed that fatty liver, a precancerous lesion caused by Pten deficiency, was strongly suppressed by the expression of INPP4B. This result suggests that phosphatidylinositol-3,4,5-trisphosphate, which abnormally accumulated due to Pten deficiency, is degraded by INPP4B, and that INPP4B substitutes for Pten function.
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Academic Significance and Societal Importance of the Research Achievements |
PTENは代表的ながん抑制遺伝子の一つである。我々はINPP4Bが、PTENと同じ基質を脱リン酸化することを見出し、PTENの機能をINPP4Bにより代替できる可能性に着目した。本研究において、新たに作製した条件付きINPP4B過剰発現マウスを用いることで、外来性のINPP4Bを発現が、Pten欠損による前がん病変(脂肪肝)の発症を抑制しうることがマウス個体レベルで初めて示された。この結果は、PTENの不活化により引き起こされるヒトのがんの発症や進展を、INPP4Bの人為的な活性化により抑制する可能性を示すものであり、INPP4Bを新たな創薬標的分子として提示するものである。
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Report
(5 results)
Research Products
(11 results)
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[Journal Article] Increased fatty acyl saturation of phosphatidylinositol phosphates in prostate cancer progression.2019
Author(s)
Koizumi A, Narita S, Nakanishi H, Ishikawa M, Eguchi S, Kimura H, Takasuga S, Huang M, Inoue T, Sasaki J, Yoshioka T, Habuchi T, Sasaki T.
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Journal Title
Sci Rep.
Volume: 9
Pages: 13257-13257
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] PIKfyve regulates melanosome biogenesis2018
Author(s)
Liggins Marc C.、Flesher Jessica L.、Jahid Sohail、Vasudeva Priya、Eby Victoria、Takasuga Shunsuke、Sasaki Junko、Sasaki Takehiko、Boissy Raymond E.、Ganesan Anand K.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Book] 脂質クオリティ2018
Author(s)
高須賀俊輔・佐々木雄彦(編集=有田誠)
Total Pages
220
Publisher
羊土社
ISBN
9784758103718
Related Report