2016 Fiscal Year Final Research Report
Search for miRNAs that regulate stemness of breast cancer stem cell to find therapeutic targets of triple-negative breast cancer.
Project/Area Number |
26430109
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Tumor biology
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Research Institution | Chiba University (2016) The University of Tokyo (2014-2015) |
Principal Investigator |
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Keywords | microRNA / microRNA inhibitor / 癌幹細胞 / EMT / 乳癌 / トリプルネガティブ |
Outline of Final Research Achievements |
Triple negative breast cancer cell line SUM149PT is composed of 2 subpopulations; epithelial-like EpCAM positive (EpCAM+) cells and mesenchymal-like EpCAM negative (EpCAM-) cells. In this study, we found that EpCAM+ cells had strong tumorigenicity and the expression levels of miR-200 family were high in only EpCAM+ cells. When we suppressed the miR-200 family in EpCAM+ cells, conversion of EpCAM+ cells to EpCAM- cells occurred and the tumorigenicity of the EpCAM+ cells was reduced. Furthermore, we developed and used doxycycline-inducible miRNA inhibitory vector to construct EpCAM+ cell in which the activities of miR-200 family can be regulated by doxycycline. After tumor formation in xenograft mice transplanted with these cells, we inhibited miR-200 family and observed tumor regression. These results showed that miR-200 family was promising therapeutic targets of triple negative breast cancer.
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Free Research Field |
腫瘍生物学
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