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

该研究项目的目的是分析雌激素受体(ER)变体在人类子宫内膜和子宫内膜癌中的生物学作用。为了阐明ERa的作用，我们首先研究了ERa基因表达的调控机制。结果表明，在人、猴和大鼠中都存在ERpha的多个未翻译的第一外显子和启动子系统。我们还首次证明了人类ERbeta基因中存在多个启动子系统。我们进一步分析了猴和大鼠arornatase基因的多个未翻译的第一外显子和启动子系统，并检测到了新的未翻译的第一外显子。其次，研究了孕激素受体(PR)基因在人子宫内膜和子宫内膜癌中的表达情况。因此，我们发现了新的PR基因剪接变异体和新的PR异构体。结论：ER-和PR变异体可能在人类子宫内膜和子宫内膜癌中起重要作用。然而，选择性剪接的调控机制以及变异型受体的功能仍有待阐明。现在我们正在处理这些研究。

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.