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Accepted (AM)Open Access (License Unspecified), Open
Journal article
EYA1 Phosphatase Function Is Essential to Drive Breast Cancer Cell Proliferation through Cyclin D1
Cancer research (Chicago, Ill.), v 73(14), pp 4488-4499
15 Jul 2013
PMID: 23636126
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The Drosophila Eyes Absent Homologue 1 (EYA1) is a component of the retinal determination gene network and serves as an H2AX phosphatase. The cyclin D1 gene encodes the regulatory subunits of a holoenzyme that phosphorylates and inactivates the pRb protein. Herein, comparison with normal breast showed that EYA1 is overexpressed with cyclin D1 in luminal B breast cancer subtype. EYA1 enhanced breast tumor growth in mice in vivo, requiring the phosphatase domain. EYA1 enhanced cellular proliferation, inhibited apoptosis, and induced contact-independent growth and cyclin D1 abundance. The induction of cellular proliferation and cyclin D1 abundance, but not apoptosis, was dependent upon the EYA1 phosphatase domain. The EYA1-mediated transcriptional induction of cyclin D1 occurred via the AP-1-binding site at 953 and required the EYA1 phosphatase function. The AP-1 mutation did not affect SIX1-dependent activation of cyclin D1. EYA1 was recruited in the context of local chromatin to the cyclin D1 AP-1 site. The EYA1 phosphatase function determined the recruitment of CBP, RNA polymerase II, and acetylation of H3K9 at the cyclin D1 gene AP-1 site regulatory region in the context of local chromatin. The EYA1 phosphatase regulates cell-cycle control via transcriptional complex formation at the cyclin D1 promoter. (C) 2013 AACR.
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Details
- Title
- EYA1 Phosphatase Function Is Essential to Drive Breast Cancer Cell Proliferation through Cyclin D1
- Creators
- Kongming Wu - Kimmel Cancer CenterZhaoming Li - Thomas Jefferson UniversityShaoxin Cai - Thomas Jefferson UniversityLifeng Tian - Thomas Jefferson UniversityKe Chen - Thomas Jefferson UniversityJing Wang - Tongji Medical CollegeJunbo Hu - Tongji Medical CollegeYe Sun - Boston Children's HospitalXue Li - Boston Children's HospitalAdam Ertel - Thomas Jefferson UniversityRichard G. Pestell - Thomas Jefferson University
- Publication Details
- Cancer research (Chicago, Ill.), v 73(14), pp 4488-4499
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 12
- Grant note
- R01CA070896 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) RO1CA132115; R01CA70896; R01CA75503; R01CA86072; P30CA56036 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Margaret Q. Landenberger Research Foundation Dr. Ralph and Marian C. Falk Medical Research Trust Breast Cancer Research Foundation W81XWH-11-1-0303 / Department of Defense Concept Award; United States Department of Defense
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000321823600030
- Scopus ID
- 2-s2.0-84880901185
- Other Identifier
- 991019176638904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology