| Project/Area Number |
17K10258
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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 |
Dermatology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
Funasaka Yoko 日本医科大学, 医学部, 教授 (30209150)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 悪性黒色腫 / MAPキナーゼ / 脱リン酸化 / リン酸化 / 母斑細胞 / BRAF遺伝子 / 増植制御 / BRAF変異 / NRAS変異 / BRAF / 培養細胞 / シグナル伝達 / 癌 |
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| Outline of Final Research Achievements |
We have established three cultured melanoma cell lines and nine benign nevus cell lines. The mutation of BRAFV600E was analyzed by pyrosequence method and MAP kinase related proteins were assayed using Human MAPK Pathway phosphorylation Array C-Series（RayBiotech/abcam）. Nevus cells which have mutation of BRAFV600E did not show phosphorylated state of ERK1/2 and MEK. cAMP inducer, IBMX, pituitary extracts, bFGF, ET-1, and TPA were added in these nevus cells and phosphorylated state of ERK1/2 was examined by Western blotting. Among these signal inducers, only TPA induced phosphorylated state of ERK1/2. Theses results indicate that nevus cells which have the mutation of BRAFV600E are regulated by phosphatase to keep ERK1/2 with dephosphorylated states, however this down regulation of phosphorylation of ERK1/2 are suppressed by TPA.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性黒色腫の治療にBRAFV600EとMEK阻害剤の併用療法が用いられている。今回我々は増殖制御がされている良性の母斑細胞ではBRAFV600Eの変異があってもMAPキナーゼのリン酸化が脱リン酸化作用により抑制されていること、そしてこの抑制はフォルボールエステル（T P A）により解除されることを示した。BRAFV600Eに変異を持つ黒色腫に対し、増殖のキーシグナルとなるERK1/2の活性化を抑制する新規治療薬を開発するのに役立つ研究成果であったと考える。
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