title: Effects of perfluorinated alkyl acids on cellular responses of MCF-10A mammary epithelial cells in monolayers and on acini formation in vitro.
abstract: Perfluorinated alkyl acids (PFAAs) are stable chemicals detected in tissue and serum from various species, including humans, and have been linked to adverse health outcomes. Experimental PFAA exposure in rodents has been associated with changes in mammary gland development. The estrogen receptor (ER)-negative human breast epithelial cell line, MCF-10A, can be grown as monolayer, but also has the ability to form three-dimensional acini in vitro, reflecting aspects of mammary glandular morphogenesis. Cells were exposed to five different PFAAs, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), both in monolayer and acini cultures. In monolayer cultures only the higher concentrations of PFOS, PFNA and PFDA (400-500μM) caused a significant increase in cell death, whereas PFOA and PFUnDA had no effect. Normal acini maturation was negatively impacted by PFOS, PFNA and PFDA already at the lowest concentration tested (0.6μM). Observed effects included loss of organization of the cell clusters and absence of a hollow lumen. Overall, this study demonstrated that PFAAs can interfere with cellular events related to normal development of glandular breast tissue through ER-independent mechanisms.
authors: Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), P.O. 8146 Dep., N-0033 Oslo, Norway. Electronic address: ruth.halsne@nmbu.no.
authors: Ruth
authors: R
authors: Halsne
authors: Department of Pharmaceutical Biosciences, School of Pharmacy, Oslo University, P.O. Box 1068, N-0316 Oslo, Norway.
authors: Julia Isabel
authors: JI
authors: Tandberg
authors: Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.
authors: Viola Hélène
authors: VH
authors: Lobert
authors: Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), P.O. 8146 Dep., N-0033 Oslo, Norway.
authors: Gunn Charlotte
authors: GC
authors: Østby
authors: Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), P.O. 8146 Dep., N-0033 Oslo, Norway; Norwegian Veterinary Institute, P.O. Box 750 Sentrum, N-0106 Oslo, Norway.
authors: Even
authors: E
authors: Thoen
authors: Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), P.O. 8146 Dep., N-0033 Oslo, Norway.
authors: Erik
authors: E
authors: Ropstad
authors: Department of Production Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences (NMBU), P.O. 8146 Dep., N-0033 Oslo, Norway.
authors: Steven
authors: S
authors: Verhaegen
mesh_terms: D061354:Acinar Cells / Q000187:drug effects* / Q000502:physiology; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology*
chemical_list: D005466:Fluorocarbons
keywords: Epithelial polarisation; GM130; Perfluorodecanoic acid; Perfluorononanoic acid; Perfluorooctane sulfonate; Perfluorooctanoic acid; Perfluoroundecanoic acid; Persistent organic pollutants; β-Catenin