Transcription factors of estrogen receptor alpha in human endometrium
| Project/Area Number |
17591763
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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 |
Obstetrics and gynecology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
OTSUKI Yoshinori Osaka Medical College, Faculty of Medicine, Professor (50140166)
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| Co-Investigator(Kenkyū-buntansha) |
USHIROYAMA Takahisa Osaka Medical College, Faculty of Medicine, a part-time lecturer (20148430)
ITOU Yuko Osaka Medical College, Faculty of Medicine, Junior Associate Professor (40148432)
RI Churen Osaka Medical College, Faculty of Medicine, Assistant Professor (80319532)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,180,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥180,000)
Fiscal Year 2007: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | estrogen / receptor / Biacore / transcription / promoter / Gel Shift Assay / exponential / extrapolation / endometrium / estrogen receptor / transcription factor / uterine / phosphorylation / apoptosis / AKT / PI3K |
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| Research Abstract |
Estrogen receptor alpha (ERα), together with estradiol plays a critical role through its target molecules in control of cell growth and differentiation. The activities of ERα itself can be modulate by epidermal growth factor (EGF), insulin-like growth factor-I via the phosphatidylinostitol 3-kinase (PI3K)/AKT pathway in breast cancer cells. To clarify how ERα functions are regulated in endometrial cells, molecules related to phosphorylation of ERα were examined. It was found that the expression of phosphorylated p-Aktl/2/3 (Thr 308) was increased during the proliferative phase, but decreased in the secretory phase. On the contrary, the expression of p-Aktl/2/3 (Thr 473) was lower in the proliferative phase, but higher after entering secretory phase. Observation of the phosphorylated Erα revealed that while the expression of p-Erα (Ser 104) was constant, p-Erα (Ser 118) was shown following a cyclic pattern like that of the p-Aktl/2/3 (Thr 308).
To reveal difference between normal and cancerous glandular cells, cultured Ishikawa cells were first examined immunohistochmically. The expression pattern of phosphorylated ERα and Akt in the untreated Ishikawa cells was similar to that of the normal endometrial cells, except that the expression of p-Erα (Ser 167) was only found in Ishikawa cells. Following treatment with various inhibitors that specifically target the ErbB/PI3K/Akt pathway, it was found out that the expression of p-Erα (Ser 118) and p-Erα (Ser 168) was inhibited. Further examination showed that inhibition of PI3K or AKT, rather than ErbB could induce apoptosis that could be antagonized by the addition of estrogen, indicating a mitochondrial pathway is involved. Further study is necessary to explore functional difference of PI3K/AKT in normal and cancerous endometrial cells.
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Report
(4 results)
Research Products
(15 results)
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[Presentation] Efftcts of Raloxifene on endometrial carcinoma.2007
Author(s)
Shoko Morishima, Masahide Omchi, Tsuneto Keji, Nishiyama Koji, Hiroyuki Yamaguchi, Masanori Kanemura, Yoshito Terai, Masa-Aki Shibata, Yoshinori Otsuki
Organizer
58th Annual Meeting of the Japanese Association of Obstetrician gynecologists
Description
「研究成果報告書概要(欧文)」より
Related Report
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