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Basic and Clinical Research on Sexual Steroid Hormone Receptor Messenger Ribonucleic Acid

性类固醇激素受体信使核糖核酸的基础与临床研究

基本信息

批准号：
01440069
负责人：
KATO Junzo
金额：
$ 21.7万
依托单位：
Yamanashi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1992
项目状态：
已结题

项目摘要

Gene expression of sex steroid hormone receptor (SR) mRNA was investigated from basic and clinical points of view. In the basic study ; 1) Methodologies of detection and structural analysis of SR mRNA were established. Especially, a sensitive and quantitative reverse transcription-polymerase chain reaction assay for SR mRNAs, newly developed in this study, made it possible to detect and quantify SR mRNAs with very high sensitivity. 2) The presence and level of SR mRNAs in central and peripheral tissues were analyzed by the RT-PCR method. It was indicated that gene expression of SRs mainly regulated by the levels of those mRNAs, and SR mRNAs were widely distributed in those tissues. 3) Changes in the level of SR mRNAs in the development were further analyzed. The rat progesterone receptor cDNA was partially cloned and sequenced for the first time to analyze the gene expression of progesterone receptor (PR). The analysis of the levels of mRNAs for PR isoforms A and B revealed that PR mRNAs were individually regulated in the region-specific and developmental stage-related fashion in the developing rat brain.On the other hand, in the clinical study ; 1) Detection and structural analysis of SR mRNA in normal and abnormal human tissues were carried out. It was indicated that estrogen receptor (ER) mRNA was present in ER-negative endometrial cancer of uterus. 2) Variant type of ER mRNA was investigated in the normal endometrium endometrial cancer. It was clarified that exon deleted-ER mRNA variants, which might modulate the function of wild type ER, existed in those tissues.

从基础和临床两个角度研究性类固醇激素受体（SR）mRNA的基因表达。在基础研究方面：1）建立了SR mRNA的检测和结构分析方法。特别是，一个敏感的和定量的逆转录聚合酶链反应检测SR mRNA，在这项研究中新开发的，使得有可能检测和定量SR mRNA具有非常高的灵敏度。2)采用RT-PCR方法分析中枢和外周组织中SR mRNA的存在和水平。结果表明，SRs基因表达主要受其mRNA水平的调控，且SRs mRNA在各组织中分布广泛。3)进一步分析SR mRNA水平在发育过程中的变化。为研究孕激素受体（PR）的基因表达，首次克隆了大鼠孕激素受体cDNA的部分序列。对PR亚型A和B mRNA水平的分析表明，PR mRNA在发育大鼠脑中以区域特异性和发育阶段相关的方式受到单独调控。另一方面，在临床研究中：1）对正常和异常人体组织中SR mRNA进行检测和结构分析。表明雌激素受体（ER）mRNA在ER阴性的子宫内膜癌中存在。2)研究正常子宫内膜和子宫内膜癌组织中ER mRNA的变异类型。结果表明，在这些组织中存在可能调节野生型ER功能的外显子缺失ER mRNA变体。