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Journal of Histochemistry and Cytochemistry, Vol. 47, 1553-1562, December 1999, Copyright © 1999, The Histochemical Society, Inc.


ARTICLE

Expression of Menkes Copper-transporting ATPase, MNK, in the Lactating Human Breast: Possible Role in Copper Transport into Milk

M. Leigh Acklanda, Peter Anikijenkoa, Agnes Michalczyka, and Julian F.B. Mercera
a Deakin University, Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Burwood, Victoria, Australia

Correspondence to: M. Leigh Ackland, Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Burwood Campus, 221 Burwood Highway, Burwood, Victoria 3125, Australia.

The Menkes copper ATPase (MNK) is a copper efflux ATPase that is involved in copper homeostasis. Little is known about the intracellular localization and cell-specific function of the MNK in human tissues. To investigate a possible role for this protein in lactation, we measured its expression in sections of tissue from nonlactating and lactating human breast. Western blot analysis showed that MNK expression was greater in lactating tissue than in nonlactating tissue. By confocal immunofluorescence, the MNK was detected in luminal epithelial cells of the alveoli and ducts but not in myoepithelial cells. In the nonlactating breast epithelial cells, the MNK had a predominantly perinuclear distribution. In lactating breast tissue, the distribution of the MNK was markedly altered. Lactating epithelial cells showed a granular, diffuse pattern, which extended beyond the perinuclear region of the cell. This pattern was similar to that observed in a previous study in which cultured CHO cells were exposed to high copper concentrations. Our results suggest that relocalization of the MNK is a physiological process, which may be mediated by copper levels in the breast or by hormones and other events taking place during lactation. A vesicular pathway for copper from the Golgi into milk, similar to that of calcium, is proposed.

(J Histochem Cytochem 47:1553–1561, 1999)

Key Words: Menkes protein, human breast epithelial cells, secretion, copper


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