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ATP7B expression in human breast epithelial cells is mediated by lactational hormones

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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 Ackland
A 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 cytochemistry

Volume

56

Pagination

389 - 399

Location

Seattle, Wash.

Open access

  • Yes

ISSN

0022-1554

eISSN

1551-5044

Language

eng

Notes

First publishedin the Journal of Histochemistry and Cytochemistry by the Histochemical Society

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2008, The Histochemical Society