Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer

• DOI: 10.1371/journal.pone.0148912
• Publication Date: 2016-02-09T13:34:47Z
• Authors: Tamar Kavlashvili; Yichen Jia; Donghai Dai; Xiangbing Meng; Kristina W. Thiel; Kimberly K. Leslie; Shujie Yang
• Keywords: Progesterone receptor

Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone (PR). However, many advanced tumors lose PR expression. We recently reported that efficacy of can be significantly enhanced by combining epigenetic modulators, which we term "molecularly therapy." What remained unclear was mechanism action and if estrogen α (ERα), principle inducer PR, necessary restore functional expression via molecularly therapy. Therefore, modeled endometrial have lost both ERα generating ERα-null cancer cell lines. CRISPR-Cas9 technology used delete at genomic level. Our data demonstrate treatment histone deacetylase inhibitor (HDACi) sufficient even cells devoid ERα. studies also revealed HDACi results marked downregulation oncogene Myc. established negative transcriptional regulator Myc presence or absence ERα, contrast breast cells. First, stimulation augmented decreased Second, increased activity yet blunted mRNA protein Finally, overexpression adenoviral transduction Myc-regulated genes. Analysis Cancer Genome Atlas (TCGA) database identified an inverse correlation between levels, corresponding downstream targets SRD5A1, CDK2 CCNB1. Together, these reveal previously unanticipated relationship tumor suppressor cancer.