Abstract
The ATP-binding cassette transporter, ABCG2, has been identified as a gene of significance in the regulation of bovine lactation by a number of gene mapping studies yet its role in lactational physiology remains unclear. We have used the potent ABCG2 specific inhibitor, Ko143, to investigate role of ABCG2 in primary bovine mammary epithelial cell (BMEC) proliferation and differentiation. After incubation with Ko143, the proliferation rate of BMECs was reduced at 48 and 72 hours by up to 80% (P < 0.001), and the effect was dose-dependent (approximately 40% with 10 nM Ko143 and 80% with 20 nM Ko143). Morphological changes in BMEC mammosphere formation were not observed when co-incubated with Ko143. Our results suggested that ABCG2 plays a role in mammary epithelial cell proliferation and that functional polymorphisms in this gene may influence the cellular compartment of the mammary gland and potentially milk production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / antagonists & inhibitors
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ATP-Binding Cassette Transporters / genetics*
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Adenosine / analogs & derivatives
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Adenosine / pharmacology
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Animals
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Biotechnology
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Cattle
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Cell Differentiation / genetics
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Cell Proliferation / drug effects
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Cells, Cultured
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Diketopiperazines
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Female
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Heterocyclic Compounds, 4 or More Rings
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Lactation / genetics
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Mammary Glands, Animal / cytology*
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Mammary Glands, Animal / drug effects
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Mammary Glands, Animal / metabolism*
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Spheroids, Cellular / cytology
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Spheroids, Cellular / drug effects
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Spheroids, Cellular / metabolism
Substances
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3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester
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ATP-Binding Cassette Transporters
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Diketopiperazines
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Heterocyclic Compounds, 4 or More Rings
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Adenosine