This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laniado, M. E. Articles by Abel, P. D. Search for Related Content PubMed PubMed Citation Articles by Laniado, M. E. Articles by Abel, P. D.

American Journal of Pathology, Vol 150, 1213-1221, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro

ME Laniado, EN Lalani, SP Fraser, JA Grimes, G Bhangal, MB Djamgoz and PD Abel
Department of Surgery, Royal Postgraduate Medical School, London, United Kingdom.

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.

This article has been cited by other articles:

				J. Pu, C. D. McCaig, L. Cao, Z. Zhao, J. E. Segall, and M. Zhao EGF receptor signalling is essential for electric-field-directed migration of breast cancer cells J. Cell Sci., October 1, 2007; 120(19): 3395 - 3403. [Abstract] [Full Text] [PDF]

				W. J. Brackenbury and M. B. A. Djamgoz Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell line J. Physiol., June 1, 2006; 573(2): 343 - 356. [Abstract] [Full Text] [PDF]

				S. M. Pulukuri, C. S. Gondi, S. S. Lakka, A. Jutla, N. Estes, M. Gujrati, and J. S. Rao RNA Interference-directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity in Vivo J. Biol. Chem., October 28, 2005; 280(43): 36529 - 36540. [Abstract] [Full Text] [PDF]

				S. P. Fraser, J. K.J. Diss, A.-M. Chioni, M. E. Mycielska, H. Pan, R. F. Yamaci, F. Pani, Z. Siwy, M. Krasowska, Z. Grzywna, et al. Voltage-Gated Sodium Channel Expression and Potentiation of Human Breast Cancer Metastasis Clin. Cancer Res., August 1, 2005; 11(15): 5381 - 5389. [Abstract] [Full Text] [PDF]

				M. E Mycielska, C. P Palmer, W. J Brackenbury, and M. B. A Djamgoz Expression of Na+-dependent citrate transport in a strongly metastatic human prostate cancer PC-3M cell line: regulation by voltage-gated Na+ channel activity J. Physiol., March 1, 2005; 563(2): 393 - 408. [Abstract] [Full Text] [PDF]

				M. E. Mycielska and M. B. A. Djamgoz Citrate transport in the human prostate epithelial PNT2-C2 cell line: electrophysiological analyses J. Physiol., September 15, 2004; 559(3): 821 - 833. [Abstract] [Full Text] [PDF]

				R. Aalinkeel, M. P. N. Nair, G. Sufrin, S. D. Mahajan, K. C. Chadha, R. P. Chawda, and S. A. Schwartz Gene Expression of Angiogenic Factors Correlates with Metastatic Potential of Prostate Cancer Cells Cancer Res., August 1, 2004; 64(15): 5311 - 5321. [Abstract] [Full Text] [PDF]

				J. D. Anderson, T. P. Hansen, P. W. Lenkowski, A. M. Walls, I. M. Choudhury, H. A. Schenck, M. Friehling, G. M. Holl, M. K. Patel, R. A. Sikes, et al. Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3 Mol. Cancer Ther., November 1, 2003; 2(11): 1149 - 1154. [Abstract] [Full Text] [PDF]

				M. B. A. Djamgoz, M. Mycielska, Z. Madeja, S. P. Fraser, and W. Korohoda Directional movement of rat prostate cancer cells in direct-current electric field: involvement of voltagegated Na+ channel activity J. Cell Sci., March 9, 2002; 114(14): 2697 - 2705. [Abstract] [Full Text] [PDF]

				R. S. Hubert, I. Vivanco, E. Chen, S. Rastegar, K. Leong, S. C. Mitchell, R. Madraswala, Y. Zhou, J. Kuo, A. B. Raitano, et al. STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors PNAS, December 7, 1999; 96(25): 14523 - 14528. [Abstract] [Full Text] [PDF]

				A. D. Gruber and B. U. Pauli Tumorigenicity of Human Breast Cancer Is Associated with Loss of the Ca2+-activated Chloride Channel CLCA2 Cancer Res., November 1, 1999; 59(21): 5488 - 5491. [Abstract] [Full Text] [PDF]

				L. Soroceanu, T. J. Manning Jr, and H. Sontheimer Modulation of Glioma Cell Migration and Invasion Using Cl- and K+ Ion Channel Blockers J. Neurosci., July 15, 1999; 19(14): 5942 - 5954. [Abstract] [Full Text] [PDF]