2017 Fiscal Year Final Research Report
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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| Keywords | NOTCH1 / Oral cancer / Mutation analysis |
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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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| Free Research Field |
Oral oncology
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