2013 Fiscal Year Research-status Report
ステロイドホルモンのがん幹細胞への作用を介した放射線に対する乳腺応答の修飾
| Project/Area Number |
24710066
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| Research Institution | National Institute of Radiological Sciences |
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Principal Investigator |
GUILLAUME Vares 独立行政法人放射線医学総合研究所, 放射線防護研究センター, 研究員 (10415432)
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| Keywords | がん幹細胞 / 乳癌 / プロゲステロン / 放射線 |
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| Research Abstract |
In MCF10A cells, we demonstrated the ability of steroid hormones and ionizing radiation exposure to trigger stemness-associated miRNA regulations (such as the down-regulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant CSCs. Thus progesterone might influence radiation-induced breast cancer risk by generating tumor-initiating breast CSCs through nuclear PR-independent mechanisms, such as membrane progesterone receptors (mPRs).
We have confirmed the expression of mPRs in MCF10A cells. Because not much is known about mPRs, we are now looking to understand the molecular pathways involved in the generation of CSCs in our model.
We also started using human mammary epithelial cells (HMECs) as a better model to evaluate combined steroid hormone and radiation effects in the normal breast.
We have started first experiments of 3D matrigel culture of MCF10A and HMEC cells.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The first part of the research study is now completed and the results were published in:
Vares G, Cui X, Wang B, Nakajima T, Nenoi M. Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines. PLoS One. 2013 Oct 16;8(10):e77124.
We have started to use human primary HMECs in order to evaluate the ability of steroid hormones and progesterone to generate CSCs in a normal model.
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| Strategy for Future Research Activity |
We are now investigating the molecular pathways involved in the generation of CSCs by progesterone through mPRs. This should lead to another publication by the end of the year 2014.
Then, using the 3D matrigel organoid model currently developed, we will compare paracrine (from PR-positive luminal cells to PR-negative cells) and direct effects (through mPR in PR-negative cells), both in luminal and basal cells.
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| Expenditure Plans for the Next FY Research Funding |
We didn't use much money because we tried to rationalize our use of preexisting reagents and materials in our research group. Most of the remaining money will be used during the first quarter of the new fiscal year.
A significant part of the grant money will be dedicated to purchasing normal human mammary cells (HMECs, basal / luminal).
Depending on the results of the ongoing experiments (determination of the signaling pathways involved in mPR activity), we will purchase additional molecular biology kits and PCR array kits.
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Research Products
(3 results)
