Copper and lactational hormones influence the CTR1 copper transporter in PMC42-LA mammary epithelial cell culture models

Freestone,D, Cater,MA, Ackland,ML, Paterson,D, Howard,DL, de Jonge,MD and Michalczyk,A 2014, Copper and lactational hormones influence the CTR1 copper transporter in PMC42-LA mammary epithelial cell culture models, Journal of Nutritional Biochemistry, vol. 25, no. 4, pp. 377-387, doi: 10.1016/j.jnutbio.2013.11.011.

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Title Copper and lactational hormones influence the CTR1 copper transporter in PMC42-LA mammary epithelial cell culture models
Author(s) Freestone,D
Cater,MA
Ackland,MLORCID iD for Ackland,ML orcid.org/0000-0002-7474-6556
Paterson,D
Howard,DL
de Jonge,MD
Michalczyk,AORCID iD for Michalczyk,A orcid.org/0000-0001-5716-0783
Journal name Journal of Nutritional Biochemistry
Volume number 25
Issue number 4
Start page 377
End page 387
Total pages 11
Publisher Elsevier
Place of publication New York, NY
Publication date 2014-04
ISSN 1873-4847
Keyword(s) CTR1
Copper
Human mammary gland
Lactation
Metallothionein
X-ray fluorescence microscopy
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Nutrition & Dietetics
METHIONINE-RICH CLUSTERS
INTESTINAL CACO-2 CELLS
HUMAN-BREAST
STIMULATED ENDOCYTOSIS
MAMMALIAN-CELLS
CARCINOMA CELLS
TOXIC MILK
LINE PMC42
HCTR1
EXPRESSION
Summary Adequate amounts of copper in milk are critical for normal neonatal development, however the mechanisms regulating copper supply to milk have not been clearly defined. PMC42-LA cell cultures representative of resting, lactating and suckled mammary epithelia were used to investigate the regulation of the copper uptake protein, CTR1. Both the degree of mammary epithelial differentiation (functionality) and extracellular copper concentration greatly impacted upon CTR1 expression and its plasma membrane association. In all three models (resting, lactating and suckling) there was an inverse correlation between extracellular copper concentration and the level of CTR1. Cell surface biotinylation studies demonstrated that as extracellular copper concentration increased membrane associated CTR1 was reduced. There was a significant increase in CTR1 expression (total and membrane associated) in the suckled gland model in comparison to the resting gland model, across all copper concentrations investigated (0-50 μM). Regulation of CTR1 expression was entirely post-translational, as quantitative real-time PCR analyses showed no change to CTR1 mRNA between all models and culture conditions. X-ray fluorescence microscopy on the differentiated PMC42-LA models revealed that organoid structures distinctively accumulated copper. Furthermore, as PMC42-LA cell cultures became progressively more specialised, successively more copper accumulated in organoids (resting
Language eng
DOI 10.1016/j.jnutbio.2013.11.011
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Elsevier
Persistent URL http://hdl.handle.net/10536/DRO/DU:30068741

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