| Project/Area Number |
20K18670
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | PTEN / Cowden症候群 / iPS細胞 / PTENδ / iPSC / 癌幹細胞 |
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| Outline of Research at the Start |
家族性腫瘍症候群であるCowden症候群患者の末梢血単核球を分離、ウィルスベクターにて初期化し、疾患特異的人工多能性幹細胞（iPS細胞）を作成する。Cowden遺伝子の原因遺伝子であるPTEN遺伝子の遺伝子修復をiPSCで行い、修復前後での細胞特性を解析する。
また、口腔癌細胞株の培養上清を用いて、iPS細胞を腫瘍幹細胞に分化誘導させ、PTEN遺伝子の発現とAKTシグナル伝達経路を中心に腫瘍の発生メカニズムとを探る
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| Outline of Final Research Achievements |
As in healthy individuals, iPSCs derived from Cowden syndrome patients could be induced under serum-free culture conditions. Although the induction efficiency was higher than that of healthy controls, the establishment and maintenance of iPSCs in normal culture was similar to that of healthy controls, and there was no particular change in the growth rate or undifferentiated characteristics of iPSCs.
On the other hand, PTENα gene expression and protein expression levels were reduced by about half, indicating activation of PTEN/AKT signaling. In addition, CS-iPSCs showed increased expression of PTENδ, indicating a dependence on gene expression from the mutant allele. Although the relevance to the disease is unknown, it is suggested that some changes may be caused by the accumulation of abnormal PTENδ. attempts to repair CS-iPSCs to normal sequence were unsuccessful.
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| Academic Significance and Societal Importance of the Research Achievements |
疾患の原因となる変異アレルからの遺伝子発現様相は今後の疾患発症メカニズムの解明に寄与するものと考えられる。
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