ANALYSIS OF BIOLOGICAL ROLE OF ESTROGEN RECEPTOR VARIANTS IN HUMAN UTERINE ENDOMETRIUM AND ENDOMETRIAL CANCER.

雌激素受体变体在人类子宫内膜和子宫内膜癌中的生物学作用分析。

• 批准号: 08671879
• 负责人: HIRATA Shuji
• 金额: $ 1.66万
• 依托单位: YAMANASHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671879/
• 关键词: estrogen receptor,; progesterone receptor,; mRNA; human uterine endometrium,; endometrial cancer; variant; 子宮内膜癌; ER mRNA variants; 多重非翻訳第一エキソンならびにプロモーター機構

The aim of the research project is analysis of the biological role of the estrogen receptor (ER) variants in the human uterine endometrium and endometrial cancer. In order to clarify the role, we firstly studied the regulatory mechanism of the gene expression of the ERalpha As the results, the presence of the multiple untranslated first exon and promoters system of the ERalpha has been indicated in the human, monkey and rat. We also demonstrated the existence of the multiple promoters system in the human ERbeta gene for the first time. We further analyzed the multiple untranslated first exon and promoters system of the arornatase gene in the monkey and rat, and detected the novel untranslated first exons. Secondly, study of the presence of the variants of the progesterone receptor (PR) mRNA in the human uterine endometrium and endometrial cancer was carried out. As the results, we identified the novel splicing variants of the PR mRNA and the novel isoform of the PR mRNA.In conclusion, it is indicated that the ER- and PR variants may play some important role in the human uterine endometrium and endometrial cancer. However, it remains to be elucidated that the regulatory mechanism of the alternative splicing, and the function of the variant receptors. Now we are addressing these studies.

该研究项目的目的是分析雌激素受体（ER）变异在人类子宫内膜和子宫内膜癌中的生物学作用。为了明确其作用，我们首先研究了ERalpha基因表达的调控机制，结果表明，ERalpha在人、猴和大鼠中存在多个未翻译的第一外显子和启动子系统。我们也首次证实了erβ基因中存在多启动子系统。我们进一步分析了猴和大鼠arornatase基因的多个未翻译第一外显子和启动子系统，并检测到新的未翻译第一外显子。其次，对人子宫内膜和子宫内膜癌中孕激素受体（PR） mRNA变异的存在进行了研究。结果，我们鉴定了PR mRNA的新的剪接变体和PR mRNA的新的异构体。提示ER-和PR变异可能在人子宫内膜和子宫内膜癌的发生中起重要作用。然而，这种选择性剪接的调控机制和变异受体的功能仍有待阐明。现在我们正在讨论这些研究。

项目成果

Yamada-Mouri N,Hirata S,Kato J and Hoshi K.: "Expression and distribution of cortical type aromatase mRNA Variant in the adult rat brain." Journal of Steroid Biochemistry and Molecular Biology. 60 (5-6). 325-9 (1997)

Yamada-Mouri N、Hirata S、Kato J 和 Hoshi K.：“成年大鼠大脑中皮质型芳香酶 mRNA 变体的表达和分布。”

Kato J,Yamada-Mouri N and Hirata S.: "Structure of aromatase mRNA in the rat brain." Journal of Steroid Biochemistry and Molecular Biology. 61 (3-6). 381-5 (1997)

Kato J、Yamada-Mouri N 和 Hirata S.：“大鼠大脑中芳香酶 mRNA 的结构。”

Kato J, Hirata S, Koh T, Yamada-Mouri N, Hoshi K and Okinaga S.: "The multiple untranslated first exons and promoters system of the oestrogen receptor gene in the brain and peripheral tissues of the rat and monkey and the developing rat cerebral cortex."

Kato J、Hirata S、Koh T、Yamada-Mouri N、Hoshi K 和 Okinaga S.：“大鼠、猴子和发育中大鼠的大脑和外周组织中雌激素受体基因的多个非翻译第一外显子和启动子系统

Kato J, Yamada-Mouri N and Hirata S.: "Structure of aromatase mRNA in the rat brain." Journal of Steroid Biochemistry and Molecular Biology.61(3-6). 381-385 (1997)

Kato J、Yamada-Mouri N 和 Hirata S.：“大鼠大脑中芳香酶 mRNA 的结构。”

Hirata S, Koh T, Yamada-Mouri N and Kato J.: "The novel untranslated first exon “exon ON" of the rat estrogen receptor gene [published erratum appears in Biochemical and Biophysical Research Communications, 228(2) : 653, 1996]" Biochemical and Biophysical

Hirata S、Koh T、Yamada-Mouri N 和 Kato J.：“大鼠雌激素受体基因的新型非翻译第一个外显子“外显子 ON”[已发表的勘误表出现在《生物化学和生物物理研究通讯》，228(2) : 653, 1996 ]" 生物化学和生物物理