Oral cancer model of functional mutations in NOTCH1 and HRAS
| Project/Area Number |
15K11302
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木村 穣 東海大学, 医学部, 教授 (10146706)
青山 謙一 東海大学, 医学部, 助教 (10647530)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | NOTCH1 / Oral cancer / Mutation analysis / 口腔扁平上皮癌 / 大規模遺伝子解析 / NOTCH1変異 / HRAS変異 / 変異解析 / HRAS |
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| Outline of Final Research Achievements |
HEK293 cell lines expressing NOTCH1 wild type (WT cells) or p.A465T (A465T cells) were established. Flow cytometry indicated that NOTCH1 expression on the cell membrane was lower in A465T cells than that in WT cells. NOTCH1 and NICD were both detected by western blot in WT and A465T cells. The immunofluorescence signal for NICD was detected in the nucleus of WT cells, while it was localized mainly in the cytoplasm of A465T cells. HES1 and HEY1 mRNA expression levels were lower in A465T than in WT cells. The cell growth of WT cells was significantly higher than that of HEK293 cells (P < 0.01), while that of A465T cells was significantly lower than that of HEK293 cells (37%, P < 0.01). In a xenograft model, the tumor cell implantation rate of WT cells was 80%, while that of A465T cells was 0%.
This study indicates that NOTCH1 acts as an oncogene and that the NOTCH1 mutation (p.A465T) in the ligand-binding region causes the loss of tumorigenicity by downregulating the NOTCH1 pathway.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Saliva pH affects the sweetness sense2017
Author(s)
Ken-ichi Aoyama, Yuichiro Okino, Hiroshi Yamazaki, Rena Kojima, Masahiro Uchibori, Yasuhiro Nakanishi, Yoshihide Ota
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Journal Title
Nutrition
Volume: 35
Pages: 51-55
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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