ATP7B expression in human breast epithelial cells is mediated by lactational hormones
ATP7B expression in human breast epithelial cells is mediated by lactational hormones
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DOI：
10.1369/jhc.7a7300.2008
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发表时间：
2008-04-01
影响因子：
3.2
通讯作者：
Ackland, Margaret L.
中科院分区：
文献类型：
--
作者：
Michaiczyk, Agnes;Bastow, Edward;Ackland, Margaret L.
铜转运蛋白 ATP7B 在将铜从人类乳房分泌到乳汁中的作用此前尚未报道，尽管已知 ATP7B 的小鼠直系同源物可促进小鼠乳腺中的铜分泌。我们在此表明，ATP7B 在静息和哺乳期人类乳房的管腔上皮细胞中表达，其中它在静息上皮细胞中具有核周定位，在哺乳组织中具有弥漫性定位。 ATP713 蛋白存在于与含有乳蛋白的囊泡不同的囊泡子集中，并且除细胞核周区域外，不与门克斯 ATP 酶 ATP-7A 重叠。在培养的人乳腺系 PMC42-LA 中，用哺乳激素处理诱导 ATP7B 从核周区域重新分布到邻近但与顶端质膜不重合的区域。 ATP713 的运输依赖于铜，这表明激素诱导的 ATP7A 重新分布是通过细胞内铜的增加介导的。使用过表达 mAtp7B 蛋白的极化 PMC42-LA 细胞进行的放射性铜 ((CU)-C-64) 研究表明，该转运蛋白促进铜从细胞顶端表面流出。总之，我们的结果与 ATP7B 在人类乳腺分泌铜中的重要功能一致。
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. ATP713 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 ATP713 was copper dependent, suggesting that the hormone-induced redistribution of ATP7A was mediated through an increase in intracellular copper. Radioactive copper ((CU)-C-64) 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.