2013 Fiscal Year Final Research Report
Proliferation of breast cancer stem cells via NO/cGMP signaling pathway
| Project/Area Number |
23590322
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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 pharmacology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
KANDA Yasunari 国立医薬品食品衛生研究所, 薬理部, 室長 (70510387)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Seiichi 国立医薬品食品衛生研究所, 薬理部第三室, 室長 (10270505)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 癌幹細胞 / エストロゲン / NO / cGMP / PKG |
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| Research Abstract |
Growing evidence suggests that development of breast cancer is originated from cancer stem cells, which can be isolated by aldehyde dehydrogenase (ALDH) activity-based flow cytometry analysis. However, the growth regulation of cancer stem cells has not been fully understood. In the present study, we found that estrogen increased the size of ALDH-positive cell population in MCF-7 cells. The effect of estrogen was inhibited by the estrogen receptor (ER) antagonist ICI182780. We next examined the downstream pathway from the ER. A selective NOS inhibitor inhibited the effect of estrogen on NO production and the size of ALDH-positive cell population. In addition, 8-Br-cGMP mimicked the effect of estrogen. Taken together, these data suggest the estrogen expands breast cancer stem cells through the NO/cGMP signaling pathway.
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