A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo.
Functional expression of voltage-gated sodium channel alpha-subunits (VGSCalphas), specifically Nav1.7, is associated with strong metastatic potential in prostate cancer (CaP) in vitro. Furthermore, VGSC activity in vitro directly potentiates processes integral to metastasis. To investigate VGSCalpha expression in CaP in vivo, immunohistochemistry and real-time PCR were performed on human prostate biopsies (n>20). VGSCalpha immunostaining was evident in prostatic tissues and markedly stronger in CaP vs non-CaP patients. Importantly, RT-PCRs identified Nav1.7 as the VGSCalpha most strikingly upregulated (approximately 20-fold) in CaP, and the resultant receiver-operating characteristics curve demonstrated high diagnostic efficacy for the disease. It is concluded that VGSCalpha expression increases significantly in CaP in vivo and that Nav1.7 is a potential functional diagnostic marker.
Diss
J K J
JK
Department of Biological Sciences, Neuroscience Solutions to Cancer Research Group, Imperial College London, South Kensington Campus, London, UK.
Stewart
D
D
Pani
F
F
Foster
C S
CS
Walker
M M
MM
Patel
A
A
Djamgoz
M B A
MB
D014408:Biomarkers, Tumor; D001706:Biopsy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015222:Sodium Channels / Q000096:biosynthesis* / Q000737:chemistry; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D062556:NAV1.7 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C486866:SCN9A protein, human; D015222:Sodium Channels; D012313:RNA