Functional analysis of PHLDA3, a repressor of Akt, to elucidate the mechanism of neuroendocrine tumor development
| Project/Area Number |
17H03587
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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 |
Tumor biology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Ohki Rieko 国立研究開発法人国立がん研究センター, 研究所, 独立ユニット長 (70356252)
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| Co-Investigator(Kenkyū-buntansha) |
小嶋 基寛 国立研究開発法人国立がん研究センター, 臨床開発センター, ユニット長 (30338470)
平岡 伸介 国立研究開発法人国立がん研究センター, 中央病院, 科長 (40276217)
森実 千種 国立研究開発法人国立がん研究センター, 中央病院, 医長 (50501871)
山田 正三 (財)冲中記念成人病研究所, その他部局等, 研究員 (80260131)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 神経内分泌腫瘍 / Akt / PHLDA3 / がん抑制遺伝子 / がん遺伝子Akt / PHLDA3遺伝子 / p53 / 遺伝子 / がん |
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| Outline of Final Research Achievements |
We found that the PHLDA3 gene encodes a suppressor of the oncogene Akt and is a tumor suppressor of lung / pancreatic NET. Moreover, it was shown that cases with loss of PHLDA3 function in lung / pancreatic NET are highly malignant and the patients have poorer prognosis. Based on these findings, we tackled the following three issues. 1. Analysis of PHLDA3 gene abnormality in various NET samples, comprehensive whole exon sequence analysis, RNA-seq analysis. 2. Preparation of pancreatic NET / pituitary / thyroid NET model animals useful for preclinical studies and establishment of pancreatic NET cell lines. 3. Analysis of the relationship between PHLDA3 gene abnormalities and patient prognosis and therapeutic drug response.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、組織を超えたNET 共通のがん抑制メカニズムの解明につながるものであり、今後さらに研究を進めることで、希少がんであるNET の本態解明とそれに続く創薬や治療法の開発が加速すると予想される。
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Report
(2 results)
Research Products
(13 results)
