File(s) under permanent embargo
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
journal contribution
posted on 2023-05-19, 16:15 authored by Stewart, TA, Iman AzimiIman Azimi, Thompson, EW, Roberts-Thomson, SJ, Monteith, GREpithelial-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.
History
Publication title
Biochemical and biophysical research communicationsVolume
458Pagination
509-514ISSN
0006-291XDepartment/School
School of Pharmacy and PharmacologyPublisher
Academic Press Inc Elsevier SciencePlace of publication
525 B St, Ste 1900, San Diego, USA, Ca, 92101-4495Rights statement
Copyright 2015 Elsevier Inc.Repository Status
- Restricted