title: Alteration of mammary gland development and gene expression by in utero exposure to arsenic.
abstract: Early life exposure to estrogens and estrogen like contaminants in the environment is thought to contribute to the early onset of puberty and consequently increases the risk of developing breast cancer in the exposed female. The results of this study show that in utero exposure to the metalloestrogen arsenite altered mammary gland development prior to its effect on puberty onset. In the prepubertal gland, in utero exposure resulted in an increase in the number of mammosphere-forming cells and an increase in branching, epithelial cells, and density. In the postpubertal gland, in utero exposure resulted in the overexpression of estrogen receptor-alpha (ERα) that was due to the increased and altered response of the ERα transcripts derived from exons O and OT to estradiol. These results suggest that, in addition to advancing puberty onset, in utero exposure to arsenite alters the pre- and postpubertal development of the mammary gland and possibly, the risk of developing breast cancer.
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20007, USA.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Parodi
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC 20007, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Greenfield
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20007, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Evans
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC 20007, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Chichura
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC 20007, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Alpaugh
authors.affiliation: Department of Oncology, Georgetown University, Washington, DC 20007, USA.
authors.forename: James
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20007, USA; Department of Oncology, Georgetown University, Washington, DC 20007, USA. Electronic address: martinmb@georgetown.edu.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Martin
mesh_terms: D000367:Age Factors; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005865:Gestational Age; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation; D014621:Vagina / Q000187:drug effects / Q000254:growth & development
chemical_list: D018053:Arsenites; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; C015001:arsenite
keywords: Arsenite; Estrogen receptor-alpha; In utero; Mammary stem/progenitor cells