A role for calcium in the regulation of ATP-binding cassette, sub-family C, member 3 (ABCC3) gene expression in a model of epidermal growth factor-mediated breast cancer epithelial-mesenchymal transition

Teneale A. Stewart, Iman Azimi, Erik W. Thompson, Sarah J. Roberts-Thomson, Gregory R. Monteith

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Epithelial-mesenchymal transition (EMT), a process implicated in cancer metastasis, is associated with the transcriptional regulation of members of the ATP-binding cassette superfamily of efflux pumps, and drug resistance in breast cancer cells. Epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells is calcium signal dependent. In this study induction of EMT was shown to result in the transcriptional up-regulation of ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter superfamily, which has a recognized role in multidrug resistance. Buffering of cytosolic free calcium inhibited EGF-mediated ABCC3 increases, indicating a calcium-dependent mode of regulation. Silencing of TRPM7 (an ion channel involved in EMT associated vimentin induction) did not inhibit ABCC3 up-regulation. Silencing of the store operated calcium entry (SOCE) pathway components ORAI1 and STIM1 also did not alter ABCC3 induction by EGF. However, the calcium permeable ion channel transient receptor potential cation channel, subfamily C, member 1 (TRPC1) appears to contribute to the regulation of both basal and EGF-induced ABCC3 mRNA. Improved understanding of the relationship between calcium signaling, EMT and the regulation of genes important in therapeutic resistance may help identify novel therapeutic targets for breast cancer.

Original languageEnglish (US)
Pages (from-to)509-514
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume458
Issue number3
DOIs
StatePublished - Mar 13 2015

Bibliographical note

Funding Information:
This research was partially supported by the Australian Government National Health and Medical Research Council (NHMRC) (project grant 1022263 ), and the Queensland Cancer Council (project grant 1042819 ). EWT was funded in part by the EMPathy Breast Cancer Program of the National Breast Cancer Foundation , Australia (project grant CG-10-04 ). TAS was funded by an NHMRC Dora Lush Biomedical Research Postgraduate Scholarship ( 1039358 ).

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Keywords

  • ABCC3
  • Breast cancer
  • Calcium
  • Calcium signaling
  • Epidermal growth factor
  • Epithelial-mesenchymal transition

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