Abstract 2494: A novel tool for monitoring endogenous progesterone receptor expression by mCherry using CRISPR-Cas9 genome editing technique

Abstract

Abstract Expression of progesterone receptor (PR) is a favorable prognostic marker for multiple solid tumors. However, PR expression is reduced or lost in malignant tumors which hinders response to progesterone therapy. Thus, monitoring and restoring functional PR expression is of utmost importance to sensitize progesterone therapy in endometrial cancer. We developed a stable cell line expressing the endogenous PR gene tagged a reporter gene (Hygromycin and mCherry) with CRISPR/Cas9-mediated genome editing. This allows efficient monitoring of PR expression in its native epigenetic landscape. The reporter gene expression faithfully reflects and amplifies PR expression following treatment with histone deacetylase inhibitor, romidepsin. This reporter gene transfected cells were successfully used to screen the FDA-approved 1018 library by high throughput screening in searching of potential novel drugs that increase PR expression. This strategy provides an efficient drug screening tool that can be used to screen novel PR inducers in multiple cancer cell lines. Citation Format: Yiyang Li, Xiangbing Meng, Kuo-kuang Wen, Meng Wu, Adam Dupuy, Kimberly Leslie, Shujie Yang. A novel tool for monitoring endogenous progesterone receptor expression by mCherry using CRISPR-Cas9 genome editing technique [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2494.