| Project/Area Number |
22591422
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Gunma University |
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Principal Investigator |
HORIGUCHI Jun 群馬大学, 大学院・医学系研究科, 准教授 (70272242)
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| Co-Investigator(Kenkyū-buntansha) |
ROKUTANDA Nana 群馬大学, 医学部, 助教 (50420097)
TOKINIWA Hideaki 群馬大学, 医学部, 助教 (50455979)
KOIBUCHI Noriyuki 群馬大学, 大学院・医学系研究科, 教授 (80234681)
IWASAKI Toshiharu 群馬大学, 大学院・医学系研究科, 講師 (80375576)
小田原 宏樹 群馬大学, 医学部, 助教 (10420134)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | アロマターゼ / アンドロゲン受容体 / 乳癌 / グルココルチコイド受容体 / エストロゲン |
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| Research Abstract |
Estrogen is a key regulator of the proliferation and differentiation of breast cancer cells. In addition to the estrogen supply from the ovary, estrogen is produced locally from androgen by aromatase. However, the regulation of aromatase gene expression in breast cancer has not yet been fully clarified.Retinoic acid receptor-related orphan receptor (ROR) alpha plays an important role in the differentiation of many organs by regulating the transcription of target genes. Because aromatase and RORalpha are expressed in breast cancer, the effect of RORalpha on aromatase gene expression was studied. RORalpha significantly augmented the expression of aromatase mRNA, particularly those containing exon I.4, in MCF7 cells, and aromatase activities in T47D and MCF7 cells. RORalpha also stimulated the proliferation of these cells. Transient transfection-based reporter gene assays using the promoter at exon I.4 showed that RORalpha augmented the transcription. A series of truncated mutation studies revealed that RORalpha activated the transcription through -147 to +14 bp of the promoter I.4. Furthermore, RORalpha bound to the fragment containing -119 to -107 bp of the promoter in vitro, indicating that this region may contain a novel ROR response element. Chromatin immunoprecipitation assay showed that RORalpha bound to the region containing this site of the promoter I.4 in MCF7 cells.Moreover, we examined clinical samples and found a correlation between RORalpha and aromatase expression. These results suggest that RORalpha directly activates the aromatase expression to accelerate the local production of estrogen, which results in the proliferation of breast cancer cells.
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