title: Endocrine disruptor regulation of microRNA expression in breast carcinoma cells.
abstract: BACKGROUND
  Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells.
  
  
  RESULTS
  To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen.
  
  
  CONCLUSIONS
  We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer.
authors.affiliation: Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.
authors.forename: Syreeta L
authors.initials: SL
authors.lastname: Tilghman
authors.forename: Melyssa R
authors.initials: MR
authors.lastname: Bratton
authors.forename: H Chris
authors.initials: HC
authors.lastname: Segar
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Martin
authors.forename: Lyndsay V
authors.initials: LV
authors.lastname: Rhodes
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: John A
authors.initials: JA
authors.lastname: McLachlan
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wiese
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Nephew
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
mesh_terms: D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D003634:DDT / Q000494:pharmacology*; D052244:Endocrine Disruptors / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010636:Phenols / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003634:DDT; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D004967:Estrogens; D035683:MicroRNAs; D010636:Phenols; C524940:MIRN21 microRNA, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds