DEVELOPMENT OF AN IN VITRO ESTROGEN MODULATOR ASSAY

描述：（改编自应用程序）为了开发一个有效的， 相关的体外方法来筛选雌激素化学物质，PI已经完成了他的 目的的I期STTR和优化的MCF-7病灶形成试验。 在该II期申请中，PI建议验证MCF-7病灶检测试剂盒 使用一组已知的雌激素调节剂，并表征 雌激素调节剂在ER结合方面形成病灶的基础，或 调节代谢变化。 拟定商业应用：将应用MCF-7病灶测定 商业上用于检测和表征雌激素调节剂 环境相关的样品。此外，它还将向 制药业作为生理筛选的线索方面的雌激素 和抗雌激素活性，作为靶向终点或作为有害的副作用。 焦点测定的这些应用将弥合非生理性测定与非生理性测定之间的差距。 高通量检测和更昂贵的动物研究。雌激素的终点 依赖的融合后细胞增殖和组织重建，导致 多细胞灶的发展，具有生理相关性，因为它是基于 体内雌激素反应的体外类似物，使用 人乳腺组织来源雌激素应答MCF-7细胞系。

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.