DEVELOPMENT OF AN IN VITRO ESTROGEN MODULATOR ASSAY

体外雌激素调节剂测定的开发

基本信息

批准号：
6382258
负责人：
JOHN F GIERTHY
金额：
$ 24.99万
依托单位：
IN VITRO TECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-07-01 至 2003-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6382258
关键词：
MCF7 cell bioassay cell proliferation drug screening /evaluation environmental health environmental toxicology estrogen analog estrogen inhibitor estrogen receptors hormone regulation /control mechanism receptor binding technology /technique development tissue /cell culture toxicant screening

项目摘要

DESCRIPTION: (adapted from application) Towards developing an efficient and relevant in vitro method to screen estrogenic chemicals, the PI has finished his objectives of the Phase I STTR and optimized the MCF-7 focus formation assay. In this Phase II application, the PI proposes to validate the MCF-7 focus assay using a group of known estrogen modulators and characterize the mechanistic basis of estrogen modulators of focus formation in regard to ER binding or regulation of metabolic alterations. PROPOSED COMMERCIAL APPLICATION: The MCF-7 focus assay will be applied commercially for the detection and characterization of estrogen modulators in environmentally relevant samples. In addition, it will be marketed to the pharmaceutical industry as a physiological screen for leads with regard to estrogenic and anti estrogenic activity, either as targeted endpoints or as deleterious side effects. These applications of the focus assay will bridge the gap between non-physiological high-through-put assays and more costly animal studies. The end point of estrogen dependent postconfluent cell proliferation and tissue restructuring, resulting in the development of multicelluar foci, has physiological relevance since it is based on an in vitro analogue of the in vivo estrogenic response, using specific clones of the human breast tissue-derived estrogen-responsive MCF-7 cell line.

描述：（从应用程序改编）发展有效和与筛选雌激素化学物质的相关体外方法，PI已完成他的 I阶段STTR的目标并优化了MCF-7焦点形成测定法。在此II阶段应用中，PI提议验证MCF-7焦点测定法使用一组已知的雌激素调节剂并表征机制关于ER结合或代谢改变的调节。拟议的商业应用：将应用MCF-7焦点测定法商业上用于检测和表征雌激素调节剂与环境相关的样本。此外，它将推向制药行业是雌激素的生理屏幕和抗雌激素活性，无论是靶向终点还是有害副作用。这些焦点测定的这些应用将弥合非物理学之间的差距高直线测定法和更昂贵的动物研究。雌激素的终点依赖的富含后流体的细胞增殖和组织重组，导致多细胞病灶的开发具有生理意义，因为它是基于使用体内雌激素反应的体外类似物，使用特定的克隆人类乳腺组织衍生的雌激素响应性MCF-7细胞系。