P0229 Possible interaction between HIF-1α and VGSCS in aggressive breast cancer cells

Abstract

<h3>Background</h3> Invasion and metastasis are the leading causes of therapeutic failure and death among breast cancer patients. Tumour hypoxia promotes cancer advancement through alteration of gene expression, particularly through hypoxia-inducible factor HIF-1<i>α</i>, to maintain survivability. Voltage-gated sodium channels (VGSCs) are a new molecular diagnostic tool for selective identification of breast cancer metastatic potential and a therapeutic target for blockage of its progression. In this study, HIF-1<i>α</i> and VGSC mRNA expression was characterised in human breast cancer cell lines with different metastatic potential, and possible interactions were elucidated. <h3>Methods</h3> Conventional and semi-quantitative real-time PCR was done to validate the primers and determine the expression of HIF-1<i>α</i> and VGSC (Nav1.5 and nNav1.5) mRNA in normoxic conditions. Target gene expression was compared between a non-cancerous breast epithelial cell line (MCF-10A), a weakly metastatic breast cancer cell line (MCF-7), and an aggressive human breast cancer cell line (MDA-MB-231). <h3>Findings</h3> HIF-1<i>α</i> mRNA expression was detected in all three cell lines; expression was highest in MDA-MB-231 cells, where it was 3-fold higher than in MCF-10A cells, and was 1.6-fold higher in MCF-7 cells than in MCF-10A cells. Expression of Nav1.5 and nNav1.5 mRNA was 400-fold and 140-fold higher, respectively, in MDA-MB-321 cells than in MCF-7 cells, and Nav1.5 and nNav1.5 mRNA expression was not detected in MCF-10A cells. <h3>Interpretation</h3> This study demonstrated that upregulation of HIF-1<i>α</i> and VGSCs (Nav1.5 and nNav1.5) genes is significant in an aggressive breast cancer cell line, compared with weakly metastatic and non-cancerous cells, suggesting a possible interaction between HIF-1<i>α</i> and VGSCs in breast cancer.