The biology of zinc transport in mammary epithelial cells: Implications for mammary gland development, lactation, and involution

Nicholas H. McCormick, Stephen R. Hennigar, Kirill Kiselyov, Shannon Kelleher

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Zinc plays a critical role in a vast array of cellular functions including gene transcription, protein translation, cell proliferation, differentiation, bioenergetics, and programmed cell death. The mammary gland depends upon tight coordination of these processes during development and reproduction for optimal expansion, differentiation, and involution. For example, zinc is required for activation of matrix metalloproteinases, intracellular signaling cascades such as MAPK and PKC, and the activation of both mitochondrial-mediated apoptosis and lysosomal-mediated cell death. In addition to functional needs, during lactation the mammary gland must balance providing optimal zinc for cellular requirements with the need to secrete a substantial amount of zinc into milk to meet the requirements of the developing neonate. Finally, the mammary gland exhibits the most profound example of programmed cell death, which is driven by both apoptotic and lysosomal-mediated cell death. Two families of zinc-specific transporters regulate zinc delivery for these diverse functions. Members of the ZIP family of zinc transporters (ZIP1-14) import zinc into the cytoplasm from outside the cell or from subcellular organelles, while members of the ZnT family (ZnT1-10) export zinc from the cytoplasm. Recently, the ion channel transient receptor potential mucolipin 1 (TRPML1) has also been implicated in zinc transport. Herein, we review our current understanding of the molecular mechanisms through which mammary epithelial cells utilize zinc with a focus on the transport of zinc into discrete subcellular organelles for specific cellular functions during mammary gland development, lactation, and involution.

Original languageEnglish (US)
Pages (from-to)59-71
Number of pages13
JournalJournal of mammary gland biology and neoplasia
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2014

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Human Mammary Glands
Lactation
Zinc
Breast
Epithelial Cells
Cell Death
Organelles
Cytoplasm
Protein Biosynthesis
Matrix Metalloproteinases
Ion Channels
Energy Metabolism
Reproduction
Cell Differentiation
Milk
Cell Proliferation
Newborn Infant
Apoptosis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

McCormick, Nicholas H. ; Hennigar, Stephen R. ; Kiselyov, Kirill ; Kelleher, Shannon. / The biology of zinc transport in mammary epithelial cells : Implications for mammary gland development, lactation, and involution. In: Journal of mammary gland biology and neoplasia. 2014 ; Vol. 19, No. 1. pp. 59-71.
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The biology of zinc transport in mammary epithelial cells : Implications for mammary gland development, lactation, and involution. / McCormick, Nicholas H.; Hennigar, Stephen R.; Kiselyov, Kirill; Kelleher, Shannon.

In: Journal of mammary gland biology and neoplasia, Vol. 19, No. 1, 01.01.2014, p. 59-71.

Research output: Contribution to journalArticle

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