Activated zinc transporter ZIP7 as an indicator of anti-hormone resistance in breast cancer

Ziliotto, Silvia, Gee, Julia M. W. ORCID: https://orcid.org/0000-0001-6483-2015, Ellis, Ian O., Green, Andrew R., Finlay, Pauline, Gobbato, Anna and Taylor, Kathryn M. ORCID: https://orcid.org/0000-0002-9576-9490 2019. Activated zinc transporter ZIP7 as an indicator of anti-hormone resistance in breast cancer. Metallomics 11 (9) , pp. 1579-1592. 10.1039/C9MT00136K

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Abstract

ZIP7, a member of the ZIP family of zinc importers, resides on the endoplasmic reticulum membrane and transports zinc from intracellular stores to the cytoplasm after activation by CK2 phosphorylation on two serine residues (S275 and S276). ZIP7 is known to be required for the growth of anti-hormone resistant breast cancer models, especially those with acquired tamoxifen resistance developed from MCF-7. Using our new pS275S276ZIP7 antibody which only recognises activated ZIP7 (pZIP7), we have demonstrated that the hyperactivation of ZIP7 is prevalent in tamoxifen-resistant breast cancer cells. This evidence suggests that pZIP7 might have potential as a biomarker of acquired resistance to such anti-hormones in breast cancer, a current unmet clinical need. In this regard, we have also developed a new immunohistochemical assay for pZIP7 which allowed pZIP7 to be tested on a small clinical series of breast cancer tissues confirming its prevalence in such tumours and relationship to a variety of clinicopathological parameters and biomarkers previously associated with endocrine resistant phenotypes, notably increased activated MAPK signalling, expression of ErbB2, CD71 and the proto-oncogene c-Fos, as well as with increased tumour grade.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Additional Information:	This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.
Publisher:	Royal Society of Chemistry
ISSN:	1756-5901
Funders:	Wellcome Trust, Tenovus Cancer Care
Date of First Compliant Deposit:	10 September 2019
Date of Acceptance:	22 July 2019
Last Modified:	07 Jul 2023 03:27
URI:	https://orca.cardiff.ac.uk/id/eprint/125375

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