title: Endocrine disrupting chemical, bisphenol-A, induces breast cancer associated gene HOXB9 expression in vitro and in vivo.
abstract: HOXB9 is a homeobox-containing gene that plays a key role in mammary gland development and is associated with breast and other types of cancer. Here, we demonstrate that HOXB9 expression is transcriptionally regulated by estradiol (E2), in vitro and in vivo. We also demonstrate that the endocrine disrupting chemical bisphenol-A (BPA) induces HOXB9 expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of ovariectomized (OVX) rats. Luciferase assay showed that estrogen-response-elements (EREs) in the HOXB9 promoter are required for BPA-induced expression. Estrogen-receptors (ERs) and ER-co-regulators such as MLL-histone methylase (MLL3), histone acetylases, CBP/P300, bind to the HOXB9 promoter EREs in the presence of BPA, modify chromatin (histone methylation and acetylation) and lead to gene activation. In summary, our results demonstrate that BPA exposure, like estradiol, increases HOXB9 expression in breast cells both in vitro and in vivo through a mechanism that involves increased recruitment of transcription and chromatin modification factors.
authors.affiliation: Epigenetics Research Laboratory, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States.
authors.forename: Paromita
authors.initials: P
authors.lastname: Deb
authors.affiliation: Epigenetics Research Laboratory, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States.
authors.forename: Arunoday
authors.initials: A
authors.lastname: Bhan
authors.affiliation: Epigenetics Research Laboratory, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States.
authors.forename: Imran
authors.initials: I
authors.lastname: Hussain
authors.affiliation: Epigenetics Research Laboratory, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States.
authors.forename: Khairul I
authors.initials: KI
authors.lastname: Ansari
authors.affiliation: Department of Psychology, The University of Texas at Arlington, Arlington, TX 76019, United States.
authors.forename: Samara A
authors.initials: SA
authors.lastname: Bobzean
authors.affiliation: Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, TX 77030, United States.
authors.forename: Tej K
authors.initials: TK
authors.lastname: Pandita
authors.affiliation: Department of Psychology, The University of Texas at Arlington, Arlington, TX 76019, United States.
authors.forename: Linda I
authors.initials: LI
authors.lastname: Perrotti
authors.affiliation: Epigenetics Research Laboratory, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States. Electronic address: smandal@uta.edu.
authors.forename: Subhrangsu S
authors.initials: SS
authors.lastname: Mandal
mesh_terms: D000818:Animals; D001483:Base Sequence; D001559:Benzhydryl Compounds / Q000633:toxicity*; D001943:Breast Neoplasms / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008321:Mammary Glands, Animal / Q000473:pathology; D008954:Models, Biological; D010052:Ovariectomy; D010636:Phenols / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D018398:Homeodomain Proteins; D010636:Phenols; D011960:Receptors, Estrogen; C491257:HOXB9 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol-A; Endocrine disruption; Epigenetics; Estrogen signaling; Gene expression; HOXB9