Role of metadherin in estrogen-regulated gene expression

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

doi:10.3892/ijmm.2017.3020

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Role of metadherin in estrogen-regulated gene expression

Journal article

Open access

Peer reviewed

Role of metadherin in estrogen-regulated gene expression

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

International journal of molecular medicine, Vol.40(2), pp.303-310

08/2017

DOI: 10.3892/ijmm.2017.3020

PMCID: PMC5504974

PMID: 28627585

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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.

Cell Adhesion Molecules - genetics

Humans

Endometrial Neoplasms - metabolism

Gene Expression Regulation, Neoplastic

Cell Adhesion Molecules - metabolism

Breast Neoplasms - metabolism

Protein Interaction Maps

Breast Neoplasms - genetics

Estrogen Receptor alpha - genetics

Endometrial Neoplasms - genetics

Gene Deletion

Cell Line, Tumor

Estrogens - genetics

Estrogen Receptor alpha - metabolism

Female

Estrogens - metabolism

Details

Title: Subtitle: Role of metadherin in estrogen-regulated gene expression
Creators: Yujun Li - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Jesus Gonzalez Bosquet - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Shujie Yang - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Kristina W Thiel - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Yuping Zhang - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Haitao Liu
Kimberly K Leslie - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Xiangbing Meng - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: International journal of molecular medicine, Vol.40(2), pp.303-310
DOI: 10.3892/ijmm.2017.3020
PMID: 28627585
PMCID: PMC5504974
NLM abbreviation: Int J Mol Med
ISSN: 1107-3756
eISSN: 1791-244X
Publisher: Greece
Grant note: R01 CA099908 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA184101 / NCI NIH HHS
Language: English
Date published: 08/2017
Academic Unit: Pathology; Obstetrics and Gynecology
Record Identifier: 9983931207702771

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