2007 Fiscal Year Final Research Report Summary
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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| Keywords | estrogen / receptor / Biacore / transcription / promoter / Gel Shift Assay / exponential / extrapolation |
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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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Research Products
(14 results)
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[Presentation] 子宮内膜癌細胞に対するraloxifeneの効果2007
Author(s)
森嶌 祥子, 大道 正英, 恒遠 啓示, 西山 浩司, 山口 裕之, 金村 昌徳, 寺井 義人, 柴田 雅朗, 大槻 勝紀
Organizer
第58回日本産科婦人科学会
Place of Presentation
国立京都国際会館
Year and Date
20070414-17
Description
「研究成果報告書概要(和文)」より
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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
Year and Date
20070414-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] ヒト子宮内膜に存在するSP細胞の性状の解析2007
Author(s)
阿部 英明, 柴田 雅朗, 日下 部健, 李 忠連, 伊藤 裕子, 森嶌 祥子, 大槻 勝紀
Organizer
第112回日本解剖学会
Place of Presentation
大阪国際会議場
Year and Date
20070327-29
Description
「研究成果報告書概要(和文)」より
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