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

Stewart, Teneale A., Azimi, Iman, Thompson, Erik W., Roberts-Thomson, Sarah J., & Monteith, Gregory R. (2015) 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. Biochemical and Biophysical Research Communications, 458(3), pp. 509-514.

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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.

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ID Code: 97715
Item Type: Journal Article
Refereed: Yes
Keywords: ABCC3, Breast cancer, Calcium, Calcium signaling, Epidermal growth factor, Epithelial-mesenchymal transition, calcium ion, fibronectin, messenger RNA, multidrug resistance associated protein 1, multidrug resistance associated protein 3, multidrug resistance protein 5, nerve cell adhesion molecule, transient receptor potential channel 1, transient receptor potential channel M7, uvomorulin, vimentin, multidrug resistance protein, multidrug resistance-associated protein 3, transient receptor potential cation channel, subfamily C, member 1, transient receptor potential channel C, Article, calcium cell level, cancer cell culture, controlled study, epithelial mesenchymal transition, gene expression, immunoblotting, priority journal, real time polymerase chain reaction, reverse transcription polymerase chain reaction, upregulation, breast, breast tumor, female, gene expression regulation, genetics, human, metabolism, pathology, tumor cell line, Breast Neoplasms, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Humans, Multidrug Resistance-Associated Proteins, RNA, Messenger, TRPC Cation Channels
DOI: 10.1016/j.bbrc.2015.01.141
ISSN: 0006-291X
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 31 Jul 2016 23:03
Last Modified: 02 Aug 2016 04:16

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