Relative Expression of Voltage‐Gated Sodium Channels in Cancerous and Noncancerous Cells during the Cell Cycle

Abstract

Upregulation of voltage gated sodium channels (VGSCs) is the target for many novel carcinoma therapies. The majority carcinomas over-express voltage gated sodium channels, including breast cancers, lung cancers and mesotheliomas. We found variability in VGSC expression in clonal cancer cell lines. There is some limited electrophysiologic evidence that there is an upregulation of VGSCs during cell division. We hypothesized that the doubling of DNA during the cell cycle would also double the cell surface expression of VGSC protein compared to nondividing cells. We tested this hypothesis using flow cytometry with the fluorescent DNA label, propidium iodide and a conjugated panspecific-VGSC antibody. For lung cells, we compared A549 lung cancer cells with MRC5 control cell line and KLN 205 mouse cancer line. We compared H28 mesothelioma cells with MeT-5a normal pleural effusion cells and AB1 mouse mesothelioma cells. For breast cancer, we compared MDA-MB 231 breast cancer cells, MCF 10a control cells, and 4T1 mouse breast cancer cells. We found that, amoungst all the cell lines, there is between 1.86 and 2.15 more VGSCs expressed in dividing cells than in nondividing cells. Additionally, in cells imaged with confoccal microscopy, VGSCs were also shown in abundance at the leading ends of cells in anaphase. With this information we can more effectively target novel cancer therapies and thus improve the efficacy in carcinomas that overexpress VGSCs.