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Genes (Basel). 2017 May 15;8(5). pii: E144. doi: 10.3390/genes8050144.

DNA Methylation Targets Influenced by Bisphenol A and/or Genistein Are Associated with Survival Outcomes in Breast Cancer Patients.

Author information

1
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl, San Antonio, TX 78229, USA. Jadhav@livemail.uthscsa.edu.
2
Fox Chase Cancer Center, Temple University Health System, 333 Cottman Ave, Philadelphia, PA 19111, USA. Julia.Pereira@fccc.edu.
3
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl, San Antonio, TX 78229, USA. YaoWangPRC@hotmail.com.
4
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl, San Antonio, TX 78229, USA. jliuj6@uthscsa.edu.
5
Fox Chase Cancer Center, Temple University Health System, 333 Cottman Ave, Philadelphia, PA 19111, USA. theresa.diepnguyen@gmail.com.
6
Department of Pharmacology and Toxicology University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA. feijun@uab.edu.
7
Department of Pharmacology and Toxicology University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA. jenkinss@uab.edu.
8
Fox Chase Cancer Center, Temple University Health System, 333 Cottman Ave, Philadelphia, PA 19111, USA. Jose.Russo@fccc.edu.
9
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl, San Antonio, TX 78229, USA. huangt3@uthscsa.edu.
10
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl, San Antonio, TX 78229, USA. jinv@uthscsa.edu.
11
Department of Pharmacology and Toxicology University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA. Coral@uab.edu.

Abstract

Early postnatal exposures to Bisphenol A (BPA) and genistein (GEN) have been reported to predispose for and against mammary cancer, respectively, in adult rats. Since the changes in cancer susceptibility occurs in the absence of the original chemical exposure, we have investigated the potential of epigenetics to account for these changes. DNA methylation studies reveal that prepubertal BPA exposure alters signaling pathways that contribute to carcinogenesis. Prepubertal exposure to GEN and BPA + GEN revealed pathways involved in maintenance of cellular function, indicating that the presence of GEN either reduces or counters some of the alterations caused by the carcinogenic properties of BPA. We subsequently evaluated the potential of epigenetic changes in the rat mammary tissues to predict survival in breast cancer patients via the Cancer Genomic Atlas (TCGA). We identified 12 genes that showed strong predictive values for long-term survival in estrogen receptor positive patients. Importantly, two genes associated with improved long term survival, HPSE and RPS9, were identified to be hypomethylated in mammary glands of rats exposed prepuberally to GEN or to GEN + BPA respectively, reinforcing the suggested cancer suppressive properties of GEN.

KEYWORDS:

Bisphenol A; DNA-methylation; genistein

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