Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

β-Subunits of voltage-gated sodium channels in human prostate cancer: quantitative in vitro and in vivo analyses of mRNA expression

Prostate Cancer and Prostatic Diseases volume 11, pages 325–333 (2008)Cite this article

Abstract

We previously identified high levels of Nav1.7 voltage-gated sodium channel α-subunit (VGSCα) mRNA and protein in human prostate cancer cells and tissues. Here, we investigated auxillary β-subunit (VGSCβs) expression. In vitro, the combined expression of all four VGSCβs was significantly (∼4.5-fold) higher in strongly compared to weakly metastatic cells. This was mainly due to increased β1-expression, which was under androgenic control. In vivo, β1–β4 mRNAs were detectable and their expression in CaP vs non-CaP tissues generally reflected the in vitro levels in relation to metastatic potential. The possible role(s) of VGSCβs (VGSCα-associated and VGSCα-independent) in prostate cancer are discussed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Grimes JA, Fraser SP, Stephens GJ, Downing JE, Laniado ME, Foster CS et al. Differential expression of voltage-activated Na+ currents in two prostatic tumour cell lines: contribution to invasiveness in vitro. FEBS Letts 1995; 369: 290–294.

    Article  CAS  Google Scholar 

  2. Laniado ME, Lalani EN, Fraser SP, Grimes JA, Bhangal G, Djamgoz MB et al. Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasiveness in vitro. Am J Path 1997; 150: 1213–1221.

    CAS  PubMed  Google Scholar 

  3. Djamgoz MB, Mycielska M, Madeja Z, Fraser SP, Korohoda W . Directional movement of rat prostate cancer cells in direct-current electric field: involvement of voltage gated Na+ channel activity. J Cell Sci 2001; 114: 2697–2705.

    CAS  PubMed  Google Scholar 

  4. Fraser SP, Salvador V, Manning EA, Mizal J, Altun S, Raza M et al. Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility. J Cell Physiol 2003; 195: 479–487.

    Article  CAS  PubMed  Google Scholar 

  5. Diss JK, Archer SN, Hirano J, Fraser SP, Djamgoz MB . Expression profiles of voltage-gated Na+ channel α-subunit genes in rat and human prostate cancer cell lines. Prostate 2001; 48: 165–178.

    Article  CAS  PubMed  Google Scholar 

  6. Diss JK, Stewart D, Pani F, Foster CS, Walker MM, Patel A et al. A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo. Prostate Cancer Prostate Dis 2005; 8: 266–273.

    Article  CAS  Google Scholar 

  7. Isom LL, De Jongh KS, Patton DE, Reber BF, Offord J, Charbonneau H et al. Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science 1992; 256: 839–842.

    Article  CAS  PubMed  Google Scholar 

  8. Isom LL, Ragsdale DS, De Jongh KS, Westenbroek RE, Reber BF, Scheuer T et al. Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell 1995; 83: 433–442.

    Article  CAS  PubMed  Google Scholar 

  9. Morgan K, Stevens EB, Shah B, Cox PJ, Dixon AK, Lee K et al. beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. Proc Nat Acad Sci USA 2000; 97: 2308–2313.

    Article  CAS  PubMed  Google Scholar 

  10. Yu FH, Westenbroek RE, Silos-Santiago I, McCormick KA, Lawson D, Ge P et al. Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J Neurosci 2003; 23: 7577–7585.

    Article  CAS  PubMed  Google Scholar 

  11. Oh Y, Waxman SG . Beta 1 subunit mRNA of the rat brain Na+ channel is expressed in glial cells. Proc Natl Acad Sci USA 1994; 91: 9985–9989.

    Article  CAS  PubMed  Google Scholar 

  12. Kazen-Gillespie KA, Ragsdale DS, D'Andrea MR, Mattei LN, Rogers KE, Isom LL . Cloning, localization, and functional expression of sodium channel beta1A subunits. J Biol Chem 2000; 275: 1079–1088.

    Article  CAS  PubMed  Google Scholar 

  13. Qin N, D'Andrea MR, Lubin ML, Shafaee N, Codd EE, Correa AM . Molecular cloning and functional expression of the human sodium channel beta1B subunit, a novel splicing variant of the beta1 subunit. Eur J Biochem 2003; 270: 4762–4770.

    Article  CAS  PubMed  Google Scholar 

  14. Fahmi AI, Patel M, Stevens EB, Fowden AL, John JE, Lee K et al. The sodium channel beta-subunit SCN3b modulates the kinetics of SCN5a and is expressed heterogeneously in sheep heart. J Physiol 2001; 537: 693–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Qu Y, Curtis R, Lawson D, Gilbride K, Ge P, Di Stefano PS et al. Differential modulation of sodium channel gating and persistent sodium currents by the beta1, beta2, and beta3 subunits. Mol Cell Neurosci 2001; 18: 570–580.

    Article  CAS  PubMed  Google Scholar 

  16. Meadows LS, Chen YS, Powell AJ, Clare JJ, Ragsdale DS . Functional modulation of human brain Nav1.3 sodium channels, expressed in mammalian cells, by auxiliary beta 1, beta 2 and beta 3 subunits. Neuroscience 2002; 114: 745–753.

    Article  CAS  PubMed  Google Scholar 

  17. Vijayaragavan K, Powell AJ, Kinghorn IJ, Chahine M . Role of auxiliary beta1-, beta2-, and beta3-subunits and their interaction with Na(v)1.8 voltage-gated sodium channel. Biochem Biophys Res Commun 2004; 319: 531–540.

    Article  CAS  PubMed  Google Scholar 

  18. Chen C, Bharucha V, Chen Y, Westenbroek RE, Brown A, Malhotra JD et al. Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel beta 2-subunits. Proc Nat Acad Sci USA 2002; 99: 17072–17077.

    Article  CAS  PubMed  Google Scholar 

  19. Malhotra JD, Koopmann MC, Kazen-Gillespie KA, Fetman N, Hortsch M, Isom LL . Structural requirements for interaction of sodium channel beta 1 subunits with ankyrin. J Biol Chem 2002; 277: 26681–26688.

    Article  CAS  PubMed  Google Scholar 

  20. Xiao ZC, Ragsdale DS, Malhotra JD, Mattei LN, Braun PE, Schachner M et al. Tenascin-R is a functional modulator of sodium channel beta subunits. J Biol Chem 1999; 274: 26511–26517.

    Article  CAS  PubMed  Google Scholar 

  21. Malhotra JD, Kazen-Gillespie K, Hortsch M, Isom LL . Sodium channel beta subunits mediate homophilic cell adhesion and recruit ankyrin to points of cell-cell contact. J Biol Chem 2000; 275: 11383–11388.

    Article  CAS  PubMed  Google Scholar 

  22. Davis TH, Chen C, Isom LL . Sodium channel beta 1 subunits promote neurite outgrowth in cerebellar granule neurons. J Biol Chem 2004; 279: 51424–51432.

    Article  CAS  PubMed  Google Scholar 

  23. Kazarinova-Noyes K, Malhotra JD, McEwan DP, Mattei LN, Berglund EO, Ranscht B et al. Contactin associates with Na+ channels and increases their functional expression. J Neurosci 2001; 21: 7517–7525.

    Article  CAS  PubMed  Google Scholar 

  24. Ratcliffe CF, Westenbroek RE, Curtis R, Catterall WA . Sodium channel beta1 and beta3 subunits associate with neurofascin through their extracellular immunoglobulin-like domain. J Cell Biol 2001; 154: 427–434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Srinivasan J, Schachner M, Catterall WA . Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R. Proc Nat Acad Sci USA 1998; 95: 15753–15757.

    Article  CAS  PubMed  Google Scholar 

  26. Okegawa T, Li Y, Pong RC, Hsieh JT . Cell adhesion proteins as tumor suppressors. J Urol 2002; 167: 1836–1843.

    Article  CAS  Google Scholar 

  27. Johnson D, Montpetit ML, Stocker PJ, Bennett ES . The sialic acid component of the beta1 subunit modulates voltage-gated sodium channel function. J Biol Chem 2004; 279: 44303–44310.

    Article  CAS  PubMed  Google Scholar 

  28. Chevrier P, Vijayaragavan K, Chahine M . Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine. Br J Pharmacol 2004; 142: 576–584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Berthon P, Dimitrov T, Stower M, Cussenot O, Maitland NJ . A microdissection approach to detect molecular markers during progression of prostate cancer. Br J Cancer 1995; 72: 946–951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Moriyama N, Yamaguchi T, Takeuchi T, Sakamoto E, Ueki T, Tsujimoto G et al. Semi-quantitative evaluation of α1A-adrenoceptor subtype mRNA in human hypertrophied and non-hypertrophied prostates: regional comparison. Life Sci 1999; 64: 201–210.

    Article  CAS  PubMed  Google Scholar 

  31. Hudson DL, Guy AT, Fry P, O'Hare MJ, Watt FM, Masters JR . Epithelial cell differentiation pathways in the human prostate: identification of intermediate phenotypes by keratin expression. J Hist Cytochem 2001; 49: 271–278.

    Article  CAS  Google Scholar 

  32. Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001; 25: 402–408.

    Article  CAS  Google Scholar 

  33. De Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, Aalders TW et al. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 2002; 62: 2695–2698.

    CAS  PubMed  Google Scholar 

  34. DePrimo SE, Diehn M, Nelson JB, Reiter RE, Matese J, Fero M et al. Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome Biol 2002; 3: RESEARCH0032.1–0032.12.

    Article  Google Scholar 

  35. Corcoran NM, Costello AJ . Interleukin-6: minor player or starring role in the development of hormone-refractory prostate cancer? BJU Int 2003; 91: 545–553.

    Article  CAS  PubMed  Google Scholar 

  36. Jo T, Nagata T, Iida H, Imuta H, Iwasawa K, Ma J et al. Voltage-gated sodium channel expressed in cultured human smooth muscle cells: involvement of SCN9A. FEBS Lett 2004; 567: 339–343.

    Article  CAS  PubMed  Google Scholar 

  37. Gosling M, Harley SL, Turner RJ, Carey N, Powell JT . Human saphenous vein endothelial cells express a tetrodotoxin-resistant, voltage-gated sodium current. J Biol Chem 1998; 273: 21084–21090.

    Article  CAS  PubMed  Google Scholar 

  38. Estacion M . Characterization of ion channels seen in subconfluent human dermal fibroblasts. J Physiol 1991; 436: 579–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Fraser SP, Diss JK, Lloyd LJ, Pani F, Chioni AM, George AJ et al. T-lymphocyte invasiveness: control by voltage-gated Na+ channel activity. FEBS Lett 2004; 569: 191–194.

    Article  CAS  PubMed  Google Scholar 

  40. Hinson AW, Gu XQ, Dib-Hajj S, Black JA, Waxman SG . Schwann cells modulate sodium channel expression in spinal sensory neurons in vitro. Glia 1997; 21: 339–349.

    Article  CAS  PubMed  Google Scholar 

  41. Shcherbatko A, Ono F, Mandel G, Brehm P . Voltage-dependent sodium channel function is regulated through membrane mechanics. Biophys J 1999; 77: 1945–1959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vijayaragavan K, O'Leary ME, Chahine M . Gating properties of Na(v)1.7 and Na(v)1.8 peripheral nerve sodium channels. J Neurosci 2001; 21: 7909–7918.

    Article  CAS  PubMed  Google Scholar 

  43. Bennett ES, Smith BA, Harper JM . Voltage-gated Na+ channels confer invasive properties to human prostate cancer cells. Pflugers Arch 2004; 447: 908–914.

    Article  CAS  PubMed  Google Scholar 

  44. Lenkowski PW, Shah BS, Dinn AE, Lee K, Patel MK . Lidocaine block of neonatal Nav1.3 is differentially modulated by co-expression of beta1 and beta3 subunits. Eur J Pharmacol 2003; 467: 23–30.

    Article  CAS  PubMed  Google Scholar 

  45. Adachi K, Toyota M, Sasaki Y, Yamashita T, Ishida S, Ohe-Toyota M et al. Identification of SCN3B as a novel p53-inducible proapoptotic gene. Oncogene 2004; 23: 7791–7798.

    Article  CAS  PubMed  Google Scholar 

  46. Van Bokhoven A, Varella-Garcia M, Korch C, Johannes WU, Smith EE, Miller HL et al. Molecular characterization of human prostate carcinoma cell lines. Prostate 2003; 57: 205–225.

    Article  CAS  PubMed  Google Scholar 

  47. Culig Z, Klocker H, Bartsch G, Hobisch A . Androgen receptors in prostate cancer. Endocr Relat Cancer 2002; 9: 155–170.

    Article  CAS  Google Scholar 

  48. Wada A . Roles of voltage-dependent sodium channels in neuronal development, pain, and neurodegeneration. J Pharmacol Sci 2006; 102: 253–268.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by the Pro Cancer Research Fund (PCRF). We thank Dr Rory Curtis (Elixir Pharmaceuticals) for his comments on the manuscript and Petros Andrikopoulos for his assistance with the real-time PCR experiments.

Author information

Authors and Affiliations

  1. Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK

    J K J Diss & D S Latchman

  2. Division of Cell and Molecular Biology, Neuroscience Solutions to Cancer Research Group, Imperial College London, London, UK

    J K J Diss, S P Fraser & M B A Djamgoz

  3. Department of Histopathology, Imperial College School of Medicine, St Mary's Hospital, Norfolk Place, London, UK

    M M Walker & A Patel

  4. Department of Urology, St Mary's Hospital, Imperial College School of Medicine, London, UK

    A Patel

Authors
  1. J K J Diss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S P Fraser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M M Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D S Latchman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M B A Djamgoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J K J Diss.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Diss, J., Fraser, S., Walker, M. et al. β-Subunits of voltage-gated sodium channels in human prostate cancer: quantitative in vitro and in vivo analyses of mRNA expression. Prostate Cancer Prostatic Dis 11, 325–333 (2008). https://doi.org/10.1038/sj.pcan.4501012

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4501012

Keywords

This article is cited by

Search

Advanced search

Quick links