2004 Fiscal Year Final Research Report Summary
The expression and significance of sex steroid recepfor cofactors in the pafhogenesis of endometrial carcinoma
| Project/Area Number |
15591737
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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 | Shinshu University School of Medicine |
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Principal Investigator |
OKA Kenji Shinshu University, School of Medicine, assistant professor, 医学部附属病院, 助手 (40345749)
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| Co-Investigator(Kenkyū-buntansha) |
SHIOZAWA Tanri Shinshu University, School of Medicine, Instructor, 医学部附属病院, 講師 (20235493)
KONISHI Ikuo Shinshu University, School of Medicine, professor, 医学部, 教授 (90192062)
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| Project Period (FY) |
2003 – 2004
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| Keywords | endometrium / endometrial carcinoma / immortalization / large T antigen / telomerase / subtraction / microarray |
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| Research Abstract |
The normal endometrial glands and a subset of endometrial carcinomas express estrogen receptors (ER) and progesterone receptors (PR), and the growth of these tissues is stimulated by estrogen and suppressed by progesterone. However, the molecular mechanisms of the steroid hormone-dependent growth control have not fully been understood. In the present study, we have investigated the expression and the functional involvement of steroid receptor coactivators (SRC-1 and p300/CBP) and steroid receptor corepressors (SMRT and NCoR), which are known to mediate the growth signals from ER/PR, in sex steroid hormone-dependent growth of the normal endometrium and endometrial carcinoma. We first examined the immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR) and above-mentioned four cofactors normal endometrial glands. The results showed that the expression of ER/PR, SRC-1 and p300/CBP was predominantly observed in the proliferative phase endometria, but the expres
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sion of SMRT and NCoR was negligible. We then examined the functional contribution of coactivators using immunoprecipitation analysis. The results indicated that ER formed complex with SRC-1 in. the proliferative phase endometrtia, and with p300/CBP throughout the menstrual phases, suggesting that these complexes are involved in the estrogen-induced growth of normal endometrium. We then examined the immunohistochemical expression of the cofactors in endometrial carcinoma. The expression of ER/PR as well as SRC-1 and p300/CBP was decreased in endometrial carcinomas compared to normal endometria. In addition, the topological distribution of ER/PR was not correlated with those of SRC-1 and p300/CBP, indicating the dissociation between the expression of ER/PR, SRC-1 and p300/CBP. We therefore concluded that the dissociation of the expression between ER/PR and coactivator may be responsible for the relative refractoriness of the ER/PR-positive endometrial carcinomas to estrogen and progesterone. Less
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Research Products
(8 results)
