title: Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro.
abstract: Ion channels are important for many cellular functions and disease states including cystic fibrosis and multidrug resistance. Previous work in the Dunning rat model of prostate cancer has suggested a relationship between voltage-activated Na+ channels (VASCs) and the invasive phenotype in vitro. The objectives of this study were to 1) evaluate the expression of VASCs in the LNCaP and PC-3 human prostate cancer cell lines by Western blotting, flow cytometry, and whole-cell patch clamping, 2) determine their role in invasion in vitro using modified Boyden chambers with and without a specific blocker of VASCs (tetrodotoxin). A 260-kd protein representing VASCs was found only in the PC-3 cell line, and these were shown to be membrane expressed on flow cytometry. Patch clamping studies indicated that functional VASCs were present in 10% of PC-3 cells and blocking these by tetrodotoxin (600 nmol/L) reduced their invasiveness by 31% (P = 0.02) without affecting the invasiveness of the LNCaP cells. These results indicate that the reduction of invasion is a direct result of VASC blockade and not a nonspecific action of the drug. This is the first report of VASCs in a human prostatic cell line. VASCs are present in PC-3 but not LNCaP cells as determined by both protein and functional studies. Tetrodotoxin reduced the invasiveness of PC-3 but not LNCaP cells, and these data suggest that ion channels may play an important functional role in tumor invasion.
authors.affiliation: Department of Surgery, Royal Postgraduate Medical School, London, United Kingdom.
authors.forename: M E
authors.initials: ME
authors.lastname: Laniado
authors.forename: E N
authors.initials: EN
authors.lastname: Lalani
authors.forename: S P
authors.initials: SP
authors.lastname: Fraser
authors.forename: J A
authors.initials: JA
authors.lastname: Grimes
authors.forename: G
authors.initials: G
authors.lastname: Bhangal
authors.forename: M B
authors.initials: MB
authors.lastname: Djamgoz
authors.forename: P D
authors.initials: PD
authors.lastname: Abel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D015194:Diffusion Chambers, Culture; D004594:Electrophysiology; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D018408:Patch-Clamp Techniques; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D015222:Sodium Channels / Q000096:biosynthesis* / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D015222:Sodium Channels; D013779:Tetrodotoxin