dc.creatorMiret, Noelia Victoria
dc.creatorRico Leo, Eva
dc.creatorPontillo, Carolina Andrea
dc.creatorZotta, Elsa
dc.creatorFernández Salguero, Pedro
dc.creatorRandi, Andrea Silvana
dc.date.accessioned2018-06-14T14:48:59Z
dc.date.available2018-06-14T14:48:59Z
dc.date.created2018-06-14T14:48:59Z
dc.date.issued2017-11
dc.identifierMiret, Noelia Victoria; Rico Leo, Eva; Pontillo, Carolina Andrea; Zotta, Elsa; Fernández Salguero, Pedro; et al.; A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling; Academic Press Inc Elsevier Science; Toxicology and Applied Pharmacology; 334; 11-2017; 192-206
dc.identifier0041-008X
dc.identifierhttp://hdl.handle.net/11336/48626
dc.identifierCONICET Digital
dc.identifierCONICET
dc.description.abstractHexachlorobenzene (HCB) is a widespread environmental pollutant and a dioxin-like compound that binds weakly to the aryl hydrocarbon receptor (AhR). Because AhR and transforming growth factor β1 (TGF-β1) converge to regulate common signaling pathways, alterations in this crosstalk might contribute to developing preneoplastic lesions. The aim of this study was to evaluate HCB action on TGF-β1 and AhR signaling in mouse mammary gland, through AhR +/+ and AhR −/− models. Results showed a differential effect in mouse mammary epithelial cells (NMuMG), depending on the dose: 0.05 μM HCB induced cell migration and TGF-β1 signaling, whereas 5 μM HCB reduced cell migration, promoted cell cycle arrest and stimulated the dioxin response element (DRE) -dependent pathway. HCB (5 μM) enhanced α-smooth muscle actin expression and decreased TGF-β receptor II mRNA levels in immortalized mouse mammary fibroblasts AhR +/+, resembling the phenotype of transformed cells. Accordingly, their conditioned medium was able to enhance NMuMG cell migration. Assays in C57/Bl6 mice showed HCB (3 mg/kg body weight) to enhance ductal hyperplasia, cell proliferation, estrogen receptor α nuclear localization, branch density, and the number of terminal end buds in mammary gland from AhR +/+ mice. Primary culture of mammary epithelial cells from AhR +/+ mice showed reduced AhR mRNA levels after HCB exposure (0.05 and 5 μM). Interestingly, AhR −/− mice exhibited an increase in ductal hyperplasia and mammary growth in the absence of HCB treatment, thus revealing the importance of AhR in mammary development. Our findings show that environmental HCB concentrations modulate AhR and TGF-β1 signaling, which could contribute to altered mammary branching morphogenesis, likely leading to preneoplastic lesions and retaining terminal end buds.
dc.languageeng
dc.publisherAcademic Press Inc Elsevier Science
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.taap.2017.09.012
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0041008X17303848
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectAryl Hydrocarbon Receptor
dc.subjectEndocrine Disruptor
dc.subjectHexachlorobenzene
dc.subjectMouse Mammary Gland
dc.subjectTransforming Growth Factor Β1
dc.titleA dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


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