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Prostate. 2001 Aug 1;48(3):165-78.

Expression profiles of voltage-gated Na(+) channel alpha-subunit genes in rat and human prostate cancer cell lines.

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Department of Biology, Neurobiology Group, Sir Alexander Fleming Building, Imperial College of Science, Technology, and Medicine, London, United Kingdom.



Voltage-gated Na(+) channel (VGSC) activity has been implicated in prostate cancer (PC) metastasis. Although VGSCs can occur as multiple-subunit assemblies, the alpha-subunits (VGSCalphas) alone can encode functional channels. The VGSCalpha gene(s) responsible for the functional VGSCalpha expression in strongly metastatic PC cell lines is not known.


Two reverse transcription-PCR (RT-PCR) methods, degenerate primer screening and a novel semi quantitative PCR (SQT-PCR) technique, were used. These methods enabled a detailed qualitative and quantitative investigation of VGSCalpha mRNA expression in rat (MAT-LyLu/AT-2) and human (PC-3/LNCaP) PC cells of markedly different metastatic potential.


Expression of eight different VGSCalpha genes (SCN1A-4A, SCN7A-9A, and SCN11A) was determined in the PC cell lines. Most were expressed as multiple splice variants. SQT-PCR results were consistent with a basal level of VGSCalpha mRNA expression occurring in weakly metastatic (AT-2/LNCaP) cells, and this being greatly elevated in cells of stronger metastatic potential (MAT-LyLu/PC-3), primarily due to the elevated expression of the SCN9A gene (also termed PN1/hNe-Na).


(1) Several VGSCalpha genes and their splice variants are expressed similarly in both rat and human PC cell lines. (2) Expression levels are much higher in the strongly metastatic (MAT-LyLu/PC-3) cells. (3) Levels of SCN9A mRNA specifically are predominant in MAT-LyLu and PC-3 cells; thus, SCN9A is highly likely to be the main source of the functional VGSC detected.

[Indexed for MEDLINE]

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