Assessment of gene expression of intracellular calcium channels, pumps and exchangers with epidermal growth factor-induced epithelial-mesenchymal transition in a breast cancer cell line

Davis, F.M., Parsonage, M.T., Cabot, P.J., Parat, M.O., Thompson, E.W., Roberts-Thomson, S.J., & Monteith, G.R. (2013) Assessment of gene expression of intracellular calcium channels, pumps and exchangers with epidermal growth factor-induced epithelial-mesenchymal transition in a breast cancer cell line. Cancer Cell International, 13(72).

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Abstract

Background

Epithelial-mesenchymal transition (EMT) is a process implicated in cancer metastasis that involves the conversion of epithelial cells to a more mesenchymal and invasive cell phenotype. In breast cancer cells EMT is associated with altered store-operated calcium influx and changes in calcium signalling mediated by activation of cell surface purinergic receptors. In this study, we investigated whether MDA-MB-468 breast cancer cells induced to undergo EMT exhibit changes in mRNA levels of calcium channels, pumps and exchangers located on intracellular calcium storing organelles, including the Golgi, mitochondria and endoplasmic reticulum (ER).

Methods

Epidermal growth factor (EGF) was used to induce EMT in MDA-MB-468 breast cancer cells. Serum-deprived cells were treated with EGF (50 ng/mL) for 12 h and gene expression was assessed using quantitative RT-PCR.

Results and conclusions

These data reveal no significant alterations in mRNA levels of the Golgi calcium pump secretory pathway calcium ATPases (SPCA1 and SPCA2), or the mitochondrial calcium uniporter (MCU) or Na+/Ca2+ exchanger (NCLX). However, EGF-induced EMT was associated with significant alterations in mRNA levels of specific ER calcium channels and pumps, including (sarco)-endoplasmic reticulum calcium ATPases (SERCAs), and inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RYR) calcium channel isoforms. The most prominent change in gene expression between the epithelial and mesenchymal-like states was RYR2, which was enriched 45-fold in EGF-treated MDA-MB-468 cells. These findings indicate that EGF-induced EMT in breast cancer cells may be associated with major alterations in ER calcium homeostasis.

Impact and interest:

10 citations in Scopus
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11 citations in Web of Science®

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ID Code: 71135
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By (since 1996):1
Export Date: 6 May 2014
Source: Scopus
Art. No.: 76
Funding Details: 569645, NHMRC, National Health and Medical Research Council
Funding Details: 1022263, NHMRC, National Health and Medical Research Council
Funding Details: 1027527, NHMRC, National Health and Medical Research Council
Funding Details: National Breast Cancer Foundation
Keywords: Breast cancer calcium, EMT, IP3R, MCU, NCLX, RYR, SERCA, SPCA
DOI: 10.1186/1475-2867-13-76
ISSN: 1475-2867
Copyright Owner: Copyright 2013 Davis et al.; licensee BioMed Central Ltd.
Copyright Statement: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Deposited On: 07 May 2014 02:58
Last Modified: 08 May 2014 01:55

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