TCDD exposure disrupts mammary epithelial cell differentiation and function.
Mammary gland growth and differentiation during pregnancy is a developmental process that is sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a widespread environmental contaminant and a potent ligand for the aryl hydrocarbon receptor (AhR). We demonstrate reduced beta-casein protein induction in mouse mammary glands and in cultured SCp2 mammary epithelial cells following exposure to TCDD. SCp2 cells exposed to TCDD also show reduced cell clustering and less alveolar-like structure formation. SCp2 cells express transcriptionally active AhR, and exposure to TCDD induces expression of the AhR target gene CYP1B1. Exposure to TCDD during pregnancy reduced expression of the cell adhesion molecule E-cadherin in the mammary gland and decreased phosphorylation of STAT5, a known regulator of beta-casein gene expression. These data provide morphological and molecular evidence that TCDD-mediated AhR activation disrupts structural and functional differentiation of the mammary gland, and present an in vitro model for studying the effects of TCDD on mammary epithelial cell function.
Collins
Loretta L
LL
Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Avenue, Rochester, NY, USA.
Lew
Betina J
BJ
Lawrence
B Paige
BP
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1; D015536:Down-Regulation; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D001189:Aryl Hydrocarbon Hydroxylases; D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D002364:Caseins; D065633:Cytochrome P-450 CYP1B1; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D050799:STAT5 Transcription Factor; C484722:Ahr protein, mouse; C585498:Cyp1b1 protein, mouse