Abstract
Voltage-gated sodium channels (VGSCs) are expressed not only in excitable cells but also in numerous metastatic cells, particularly in certain types of cancer cells. In some types of cancer, including prostate cancer, the expression of VGSCs is associated with cancer migration, invasion and metastasis in vivo. However, the detailed expression profiles of VGSC α subunits in normal human prostate, in prostatic hyperplasia and prostatic cancer remain controversial. In the present study, quantitative polymerase chain reaction was used to systematically detect all subtypes of VGSC α subunits in normal human prostate, benign prostatic hyperplasia (BPH) and prostate cancer cells. The expression profile of VGSC α subunits was observed to differ between these cell types. Nav1.5 was the major isoform expressed in normal human prostate tissue, while Nav1.5 and Nav1.2 were the predominant isoforms in BPH tissue. However, in PC-3 and LNCaP cells, two typical prostate cancer cell lines, Nav1.6 and Nav1.7 were abundantly expressed. By comparing the relative expression levels of Nav1.5, Nav1.6 and Nav1.7 in these cells, the mRNA levels of Nav1.6 and Nav1.7 were identified to be 6- to 27-fold higher in PC-3 and LNCaP cells than in either normal or BPH samples (P<0.05); however, Nav1.5 mRNA levels were relatively lower compared with those of Nav1.6 or Nav1.7 in all cells analyzed. To confirm whether Nav1.6 and Nav1.7 expression in cancer cells was functional, a patch-clamp technique was used to record whole-cell currents. A tetrodotoxin-sensitive sodium current was successfully recorded in PC-3 cells, but not in LNCaP cells. It was concluded that although all types of VGSC α subunits exhibited low expression levels in normal prostate and BPH cells, both Nav1.6 and Nav1.7 were significantly upregulated in the prostate cancer cell lines, suggesting these subtypes may be potential diagnostic markers and therapeutic targets for certain types of prostate cancer in humans.
Highlights
Voltage‐gated sodium channels (VGSCs) are responsible for the rising phase of the action potential in the majority of electrically excitable cells and, are important in impulse generation and propagation [1]
In normal prostate (NP) samples, with the exception of Nav1.8, all subtypes of VGSC α subunits were detected by quantitative polymerase chain reaction (qPCR)
It has been reported that certain types of VGSC α subunits were expressed in human and rodent prostate cancer cells [10,11,12,13]
Summary
Voltage‐gated sodium channels (VGSCs) are responsible for the rising phase of the action potential in the majority of electrically excitable cells and, are important in impulse generation and propagation [1]. Nine sodium channel α subunits (Nav1.1‐Nav1.9), encoded by the SCN1A‐SCN5A and SCN8A‐SCN11A genes, have been found in vertebrates [2]. Different VGSC α subunits are abundantly expressed in the majority of excitable tissues. The functions of VGSCs in such excitable tissues are well understood. Dysfunction of VGSCs leads to several diseases in excitable tissues, including Brugada syndrome [3,4], long QT syndrome [5], chronic pain syndromes [6] and epilepsy [7]. VGSCs have been found to have relatively high expression levels in a range of cell types that are considered ‘non‐excitable’, including immune cells, fibroblasts and cancer cells [8]
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