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A model of secreting murine mammary epithelial HC11 cells comprising endogenous Bcrp/Abcg2 expression and function

Tallkvist, Jonas and Yagdiran, Yagmur and Danielsson, Louise and Oskarsson, Agneta (2015). A model of secreting murine mammary epithelial HC11 cells comprising endogenous Bcrp/Abcg2 expression and function. Cell biology and toxicology. 31:2, 111-120
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Official URL: http://dx.doi.org/10.1007/s10565-015-9298-5

Abstract

Breast cancer resistance protein (Bcrp/Abcg2) and multidrug transporter 1 (Mdr1/Abcb1) are efflux proteins located in the apical membrane of mammary epithelial cells (MEC). Bcrp is induced in MEC during gestation and lactation, while Mdr1 is down-regulated during lactation. Numerous drugs and toxic compounds are known to be actively secreted into milk by Bcrp, but most chemicals have not been investigated in this respect, emphasizing the need for functional Bcrp studies in an established cell line with secreting mammary epithelial cells. The present study was undertaken to examine expressions of Bcrp and Mdr1 in mammary epithelial HC11 cells, derived from a mid-gestational murine mammary gland. In addition, Bcrp function was assessed by transport experiments with mitoxantrone (MX) in undifferentiated HC11 cells, in HC11 cells subjected to Bcrp RNA interference (RNAi) as well as in HC11 cells stimulated to differentiate by treatment with lactogenic hormones. Differentiated HC11 cells organized into alveolar-resembling structures and gene expression of the major milk protein B-casein was induced, whereas undifferentiated cells formed monolayers with lower B-casein expression. Bcrp and Mdr1 gene and protein were expressed in both undifferentiated and differentiated HC11 cells. Differentiation of HC11 cells resulted in increased Bcrp protein expression, while Mdr1 gene and protein expressions were reduced. The Bcrp inhibitor elacridar (GF120918) reduced secretion and increased accumulation of MX in both undifferentiated and differentiated HC11 cells. Silencing of the Bcrp gene caused an increased accumulation of MX. The results indicate that the HC11 cell model provides a promising tool to investigate transport of potential Bcrp substrates in mammary epithelial cells.

Authors/Creators:Tallkvist, Jonas and Yagdiran, Yagmur and Danielsson, Louise and Oskarsson, Agneta
Title:A model of secreting murine mammary epithelial HC11 cells comprising endogenous Bcrp/Abcg2 expression and function
Series/Journal:Cell biology and toxicology (0742-2091)
Year of publishing :20 March 2015
Depositing date:2 July 2015
Volume:31
Number:2
Page range:111-120
Publisher:Springer
ISSN:0742-2091
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Accepted version
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X38 Human medicine, health, and safety
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Pathobiology
Agrovoc terms:neoplasms, drugs, drug resistance
Keywords:active transport, BCRP, Mammary epithelial HC11 cells, Mdr1, Mitoxantrone, RNAi
URN:NBN:urn:nbn:se:slu:epsilon-e-2781
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-2781
ID Code:12360
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
Deposited By: Licentiate Yagmur Yagdiran
Deposited On:02 Jul 2015 10:52
Metadata Last Modified:20 Mar 2016 00:15

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