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ATP7B Expression in Human Breast Epithelial Cells Is Mediated by Lactational Hormones

Agnes Michalczyk, Edward Bastow, Mark Greenough, James Camakaris, David Freestone, Philip Taylor, Maria Linder, Julian Mercer and Margaret L. Ackland

Centre for Cellular and Molecular Biology, Deakin University, Burwood, Australia (AM,DF,PT,JM,MLA); Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia (EB); Department of Genetics, University of Melbourne, Parkville, Australia (MG,JC); and California State University, Fullerton, California (ML)

Correspondence to: M.L. Ackland, Centre for Cellular and Molecular Biology, Deakin University, 221 Burwood Highway, Burwood 3125, Australia. E-mail: leigha{at}deakin.edu.au

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. (J Histochem Cytochem 56:389–399, 2008)

Key Words: ATP7B • copper • mammary gland • secretion • lactational hormones

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