Abstract 3619: Role of MTDH in estrogen-regulated gene expression

Abstract

Abstract Disruption of estrogen signaling is widely associated with the development of breast, endometrial, and ovarian cancers. As a multifunctional mediator of carcinogenesis, metadherin (MTDH)/AEG-1 overexpression has been associated with numerous types of cancers, with reported roles in tumor initiation, proliferation, invasion, metastasis and chemoresistance. At the molecular level, MTDH has been shown to interact with proteins that drive tumorigenesis, including NF-κB, PLZF, BCCIPα and SND1. Through analysis of the Cancer Genome Atlas (TCGA) datasets for ER-positive endometrial and breast cancers, we found that over 25% of all gene expression correlated with MTDH. Using Affymetrix microarrays, we characterized the differences in gene expression between estrogen-treated parental and MTDH-deficient endometrial and breast cancer cells. We also explored a possible interaction between MTDH and ER by immunoprecipitation and found that MTDH and ER associated in both breast and endometrial cancer cells in response to estrogen. Reciprocal co-immunoprecipitation analysis demonstrated that acute estrogen stimulation promoted the interaction of MTDH with ER in the nucleus. These data suggest that MTDH and ERα interact in the nucleus with estrogen treatment, and MTDH/ER co-regulated genes may have functions in drug resistance, metastasis and tumor progression. Citation Format: Xiangbing Meng, Yujun Li, Jesus Gonzalez Bosquet, shujie yang, Kristina W. Thiel, Kimberly K. Leslie. Role of MTDH in estrogen-regulated gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3619. doi:10.1158/1538-7445.AM2017-3619