DEVELOPMENT OF AN IN VITRO ESTROGEN MODULATOR ASSAY

描述：(改编自应用程序)朝着开发一种高效和 相关的体外筛选雌激素化合物的方法，PI已经完成了HIS 第一阶段STTR的目标，并优化了MCF-7焦点形成试验。 在这个第二阶段的应用中，PI建议验证MCF-7焦点分析 使用一组已知的雌激素调节剂，并表征其作用机制 雌激素调节物质与雌激素受体结合形成病灶的基础 代谢变化的调节。 建议的商业应用：将应用MCF-7焦点分析 用于检测和表征雌激素调节剂的商业用途 与环境有关的样品。此外，它还将向 制药行业作为雌激素相关先导化合物的生理筛选 和抗雌激素活性，要么作为靶向终点，要么作为有害副作用。 焦点分析的这些应用将弥合非生理性的 高通量的化验和更昂贵的动物研究。雌激素的终点 依赖融合后细胞增殖和组织重建，导致 多细胞病灶的发展，具有生理相关性，因为它是基于 体外模拟体内雌激素反应，使用特定的克隆 人乳腺组织源性雌激素反应性MCF-7细胞株。

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.