Role of metadherin in estrogen-regulated gene expression

Li,Yujun; Gonzalez Bosquet,Jesus; Yang,Shujie; Thiel,Kristina  W.; Zhang,Yuping; Liu,Haitao; Leslie,Kimberly  K.; Meng,Xiangbing

doi:10.3892/ijmm.2017.3020

Role of metadherin in estrogen-regulated gene expression

Authors:
- Yujun Li
- Jesus Gonzalez Bosquet
- Shujie Yang
- Kristina W. Thiel
- Yuping Zhang
- Haitao Liu
- Kimberly K. Leslie
- Xiangbing Meng
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Affiliations: Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Published online on: June 13, 2017 https://doi.org/10.3892/ijmm.2017.3020
Pages: 303-310
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The disruption of estrogen signaling is widely associated with the development of breast, endometrial and ovarian cancers. As a multifunctional mediator of carcinogenesis, metadherin (MTDH)/astrocyte elevated gene-1 (AEG-1) overexpression has been associated with numerous types of cancer, 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 nuclear factor-κB (NF-κB), promyelocytic leukaemia zinc finger (PLZF), BRCA2- and CDKN1A (p21Cip1/Waf-1/mda-6)-interacting protein α (BCCIPα) and staphylococcal nuclease and tudor domain containing 1 (SND1). Through the analysis of the Cancer Genome Atlas (TCGA) datasets for estrogen receptor (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, to the best of our knowledge, provide the first evidence that MTDH and ERα interact in the nucleus with estrogen treatment to regulate gene expression.

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