| Project/Area Number |
25461983
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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 |
General surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
KUBO Makoto 九州大学, 大学病院, 助教 (60403961)
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| Co-Investigator(Kenkyū-buntansha) |
KATANO Mitsuo 福岡女学院看護大学, 看護学部, 学長 (10145203)
NAKANO Kenji 九州大学, 先端融合医療レドックスナビ研究拠点, 教授 (00315061)
ONISHI Hideya 九州大学, 医学研究院, 准教授 (30553276)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | トリプルネガティブ乳癌 / Notchシグナル経路 / Notch4 / Stemness / Basal-like / BRCAness / Notch経路 / 浸潤性乳菅癌 / BRCA1ness |
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| Outline of Final Research Achievements |
This study shows that NOTCH4 receptor is a potential new therapeutic target for TNBC. First, NOTCH4 inhibition reduced proliferation and invasiveness in TNBC cells and reduced tumour volume and tumourigenicity, in vivo. Second, CD24 siRNA-transfected breast cancer cells (BCCs) demonstrated higher expression of Hedgehog signaling molecule, increased anchorage-independent proliferation, and enhanced invasiveness and superior tumorigenicity. DNA microarray analysis identified STAT1 as a relationship between CD24 and SHH. CD24 siRNA-transfected BCCs with concurrent STAT1 inhibition exhibited decreased SHH expression. Finally, we focused on instability of TNBC. Of the 71 TNBCs, 59 tumors (83%) were the basal-like phenotype. The results of the MLPA assays showed that 37 (62.7%) tumors had a BRCAness. Our study proved that TNBCs involve the stemness which activates Notch signaling and the BRCAness which increases gene instability.
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