EXPRESSION AND FUNCTIONAL-ANALYSIS OF VOLTAGE-ACTIVATED NA-CANCER CELL-LINES AND THEIR CONTRIBUTION TO INVASION IN-VITRO( CHANNELS IN HUMANPROSTATE)

ion channels are important for many cellular functions and disease sta tes including cystic fibrosis and multidrug resistance Previous work i n the Dunning rat model of prostate cancer has suggested a relationshi p between voltage-activated Na+ channels (VASCs) and the invasive phen otype in vitro The objectives of this study were to 1) evaluate the ex pression of VASCs in the LNCaP and PC-3 human prostate cancer cell lin es by Western blotting, flow cytometry, and whole-cell patch camping, 2) determine their role in invasion in vitro using modified Boyden cha mbers with and without a specific blocker of VASCs (tetrodotoxin). A 2 60-kd protein representing VASCs was found only in the PC-3 cell line, and these were shown to be membrane expressed onflow 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 invasivenes s of the LNCaP cells. These results indicate that the reduction of inv asion 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 ce ll line. VASCs are present in PC-3 but not LNCaP cells as determined b y both protein and functional studies, Tetradotoxin reduced the invasi veness of PC-3 but not LNCaP cells, and these data suggest that ion ch annels may play all important functional role in tumor invasion.