| Project/Area Number |
11470047
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tohoku University |
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Principal Investigator |
SASANO Hironobu Department of Pathology, Tohoku University School of Medicine, Professor, 大学院・医学系研究科, 教授 (50187142)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kazuhiro Department of Molecular Biology, Tohoku University School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80241628)
MORIYA Takuya Department of Pathology, Tohoku University Hospital, Associate Professor, 医学部・附属病院, 助教授 (00230160)
SUZUKI Takashi Department of Pathology, Tohoku University, Research Associate, 大学院・医学系研究科, 助手 (10261629)
HARADA Nobuhiro Department of Biochemistry, Fujita Health University, Professor, 医学部, 教授 (00189705)
佐藤 信二 東北大学, 大学院・医学系研究科, 講師 (10142960)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | breast cancer / endometrial cancer / estrogen / androgen / progesterone / steroid metabolism / retinoid / receptor / steroid sulfatase / estrone sulfotransferase / 5α-reductase / 17水酸化ステロイド脱水素酵素 / 子宮内膜増殖症 / レチノイド受容体 / エストロゲン受容体 / プロゲステロン受容体 |
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| Research Abstract |
We have studied intratumoral metabolism and production of estrogens and its biological significance in estrogen dependent neoplasms including human endometrial and breast carcinoma. We first studied the activity and expression of 17β-hydroxysteroid dehydrogenase (HSD) type 1 and 2, involved in the interconversion of estrone and estrodiol. In human breast carcinoma, 17βHSD1 is dominant in both actual carcinoma cases (178 cases) and cell lines derived from breast cancer whereas in human endometrial carcinoma, 17βHSD2 is dominant in both actual carcinoma cases (102 cases) and its cell lines. These results suggest that intratumoral estrogen metabolism and actions is different between human endometrial and breast carcinoma despite the presence of estrogen receptor. We further demonstrated that the expression and activity of these enzymes are regulated by retinoids and progesterones. These results suggest the importance of these as regulators of intratumoral metabolism in these estrogen dependent neoplasms. Therefore, we then examined the expression of retinoid receptors (RAR α β and γ, RXR α β and γ) and progesterone receptors A and B in these tumors. We demonstrated that the presence of these receptors may play important roles in regulation of intratumoral 17β HSDs in human breast and endometrial carcinoma. Other important enzymes involved in intratumoral estrogen metabolism are estrogen sulfatase (STS) and estrogen sulfotransferase (EST). We therefore examined the expression of these two important enzymes in human breast carcinoma. The presence of STS in tumor was significantly associated with large tumor diameters and recurrence but that of EST exerts beneficial effects on the clinical outcome of the patients. The presence of EST turned out to be an independent prognostic factors of breast cancers.
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