研究課題/領域番号 |
19K16735
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研究種目 |
若手研究
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配分区分 | 基金 |
審査区分 |
小区分50010:腫瘍生物学関連
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研究機関 | 東京大学 |
研究代表者 |
Raja Erna 東京大学, 大学院医学系研究科(医学部), 特任研究員 (30770581)
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研究期間 (年度) |
2019-04-01 – 2020-03-31
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研究課題ステータス |
中途終了 (2019年度)
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配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2020年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
2019年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
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キーワード | BMP / glioblastoma / apoptosis / EPHA6 |
研究開始時の研究の概要 |
Although BMP acts as an inhibitor for glioblastoma progression in various pre-clinical models, its therapeutic application is not yet been achieved. We propose that one of EPHA receptor tyrosine kinases is a factor that could confer sensitivity to BMP-induced apoptosis and its high expression is correlated with better prognosis. Our data will identify factor(s) that sensitizes cells towards BMP-induced apoptosis, which may be useful as biomarker for selection of BMP-based therapy.
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研究実績の概要 |
EPHA6 sensitized glioblastoma cells for BMP-2-induced apoptosis. Inoculation of cells pre-treated with BMP-2 and EPHA6 over-expression into nude mice brain showed tumor suppression leading to longer survival, in agreement with TCGA patient data analysis.
The cooperative effect on apoptosis induction depended on the kinase activity of BMP type I receptor but was independent of EPHA6 kinase function, as tested using EPHA6 kinase inactive mutant K757R and BMP receptor inhibitor LDN193189. EPHA6 also formed a protein complex with ALK-2 BMP receptor.
Finally, RNA-sequencing results suggested that apoptosis-associated genes are up-regulated in EPHA6 over-expressing cells with potentially important downstream target genes for further study. The manuscript has been submitted and is being revised.
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