mercer-atp7bexpression-2008.pdf (2.73 MB)
ATP7B expression in human breast epithelial cells is mediated by lactational hormones
journal contribution
posted on 2008-04-01, 00:00 authored by Agnes MichalczykAgnes Michalczyk, E Bastow, M Greenough, J Camakaris, David Freestone, Philip Taylor, M Linder, Julian MercerJulian Mercer, Leigh AcklandLeigh AcklandA role for the copper transporter, ATP7B, in secretion of copper from the human breast into milk has previously not been reported, although it is known that the murine ortholog of ATP7B facilitates copper secretion in the mouse mammary gland. We show here that ATP7B is expressed in luminal epithelial cells in both the resting and lactating human breast, where it has a perinuclear localization in resting epithelial cells and a diffuse location in lactating tissue. ATP7B protein was present in a different subset of vesicles from those containing milk proteins and did not overlap with Menkes ATPase, ATP-7A, except in the perinuclear region of cells. In the cultured human mammary line, PMC42-LA, treatment with lactational hormones induced a redistribution of ATP7B from a perinuclear region to a region adjacent, but not coincident with, the apical plasma membrane. Trafficking of ATP7B was copper dependent, suggesting that the hormone-induced redistribution of ATP7A was mediated through an increase in intracellular copper. Radioactive copper (64Cu) studies using polarized PMC42-LA cells that overexpressed mAtp7B protein showed that this transporter facilitates copper efflux from the apical surface of the cells. In summary, our results are consistent with an important function of ATP7B in the secretion of copper from the human mammary gland.
History
Journal
Journal of histochemistry and cytochemistryVolume
56Issue
4Pagination
389 - 399Publisher
Histochemical SocietyLocation
Seattle, Wash.Publisher DOI
Link to full text
ISSN
0022-1554eISSN
1551-5044Language
engNotes
First publishedin the Journal of Histochemistry and Cytochemistry by the Histochemical SocietyPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2008, The Histochemical SocietyUsage metrics
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