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ROLE OF RECEPTORS IN ESTROGEN ACTION IN THE UTERUS

受体在子宫雌激素作用中的作用

基本信息

批准号：
3313137
负责人：
EUGENE R DE-SOMBRE
金额：
$ 20.89万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1981
资助国家：
美国
起止时间：
1981-08-01 至 1990-07-31
项目状态：
已结题

项目摘要

The objective is to understand the role of estrogen receptors in the regulation of uterine growth and function by elucidating the important receptor changes which occur concomitantly or are required for estrogen regulation of gene expression in target cells. This is to be accomplished by studying the steroid hormone-regulated expression of several recently characterized estrogen-dependent secretory rat endometrial proteins, correlated with estrogen-dependent receptor modulation in the same cells, documenting changes in the receptor protein with a library of monoclonal antibodies to the estrogen receptor as well as steroid binding methods. The estrogen-responsive, marker proteins of the rat endometrial epithelium will be isolated, purified and characterized and used for preparation of polyclonal and monoclonal antibodies. These marker protein antibodies will be used to identify the location and possible function of the proteins and to isolate the specific m-RNAs for the proteins. After preparation of c-DNA, detailed studies will characterize the nature of the regulation of the marker at the level of transcription and translation. The c-DNA will eventually be used to screen genomic libraries to identify the gene for the estrogen-dependent markers so that the molecular details of the receptor regulated expression of the marker can provide new insight into the estrogen regulation of gene expression in the uterus. Immunoblots, binding and fractionation studies as well as immunohistochemical assays with the monoclonal antibodies to the receptor will be used to characterize changes in the nature, content and localization of the estrogen receptor in the different types of uterine cells under various hormonal conditions. Immunomethods will be used to study the major receptor events, such as estrogen receptor synthesis, potentiation, activation, processing, recycling, degradation and receptor binding to chromatin and nuclear matrix. These studies can be expected to provide new information on changes in the estrogen receptor, not available simply from assay of estrogen-binding studies, and to improve our understanding of the molecular details of steroid hormone regulation of the individual cell types of the uterus at the molecular level. This new knowledge will be useful for better diagnosis and treatment of steroid hormone-dependent cancers and will provide useful information for the control of normal and abnormal reproductive function.

目的是了解雌激素受体在乳腺癌中的作用。调节子宫的生长和功能，阐明了重要的受体的变化，同时发生或需要雌激素调节靶细胞中的基因表达。这是要完成的通过研究类固醇激素调节的几种最近的表达，特征性雌激素依赖性分泌大鼠子宫内膜蛋白，与相同细胞中的雌激素依赖性受体调节相关，用单克隆抗体库记录受体蛋白的变化，雌激素受体的抗体以及类固醇结合方法。大鼠子宫内膜上皮雌激素反应性标志蛋白的研究将被分离、纯化和表征，并用于制备多克隆和单克隆抗体。这些标记蛋白抗体将用于鉴定蛋白质的位置和可能的功能，来分离蛋白质的特定mRNA 制备后 c-DNA，详细的研究将表征调控的性质，转录和翻译水平的标记。 c-DNA会最终用于筛选基因组文库，以鉴定雌激素依赖性标记物，这样受体的分子细节该标志物的调节表达可以提供新的见解，雌激素对子宫内基因表达的调节。免疫印迹，结合和分级研究以及免疫组织化学测定，受体的单克隆抗体将用于表征变化雌激素受体的性质、含量和定位，不同类型的子宫细胞在不同的激素条件下。免疫方法将用于研究主要的受体事件，如雌激素受体合成、增强、活化、加工，再循环，降解和受体结合染色质和核矩阵这些研究有望提供新的信息，雌激素受体的变化，不能简单地通过测定雌激素结合的研究，并提高我们的分子理解，类固醇激素调节的各个细胞类型的细节在分子水平上对子宫的影响这些新知识将有助于更好地诊断和治疗类固醇依赖性癌症，将为正常和异常的控制提供有用的信息生殖功能