International Urology and Nephrology

, Volume 41, Issue 2, pp 251–257

Differential expression of potassium ion channels in human renal cell carcinoma

  • Surbhi Wadhwa
  • Pankaj Wadhwa
  • Amit K. Dinda
  • Narmada P. Gupta
Urology - Original Article



Ether-a-go-go (EAG) or EAG-related (ERG) voltage-gated potassium ion channels are involved in tumor generation and progression. Their over- and/or misexpression has been demonstrated in various tumors, and inhibition of these channels has suppressed proliferation of various cancer cells. We investigate and compare the pattern of expression of EAG and human ERG (HERG) channels in renal cell carcinoma and “normal” renal tissue.


Tissue samples, obtained at the time of radical nephrectomy from the tumor-bearing areas, and uninvolved renal tissue were preserved in 4% paraformaldehyde and cryosectioned at 20 μm. Immunohistochemical and Western blot analysis was performed on the tumor and uninvolved kidney parenchyma by incubating with polyclonal anti-HERG 1b (Alomone Lab, Israel), anti-EAG1, and anti-EAG2. Pattern of expression of EAG/HERG channels in normal renal tissue and carcinoma were noted and compared.


The study was performed on 16 radical and four partial nephrectomy specimens (n = 20). All tumors in the cohort were clear cell renal carcinoma. Normal renal tissue was found to exhibit heterogeneous cytoplasmic positivity for EAG1 and focal HERG immunoreactivity (IR) in the proximal (PCT) and distal convoluted tubules (DCT). EAG2 IR was absent in the normal renal tissue. Clear cell RCC demonstrated a loss of HERG expression while diffuse overexpression of EAG1 and EAG2 was noted. Western blot analysis corroborated the immunohistochemical observations.


In our study both EAG1 and EAG2 potassium channels were overexpressed in clear cell renal cancer. In contrast to other adenocarcinomas, there is loss of HERG expression in clear cell RCC, which may possibly explain its chemoresistance. These ion channels may provide a potential for targeted therapy.


Kidney Carcinoma Ion channels Immunohistochemistry Western blot 


  1. 1.
    Yellen G (2002) The voltage-gated potassium channels and their relatives. Nature 419:35–42. doi:10.1038/nature00978 PubMedCrossRefGoogle Scholar
  2. 2.
    Deutsch C, Chen L (1993) Heterologous expression of specific K+ channels in T lymphocytes: functional consequences for volume regulation. Proc Natl Acad Sci USA 90:10036–10040. doi:10.1073/pnas.90.21.10036 PubMedCrossRefGoogle Scholar
  3. 3.
    Wonderlin WF, Strobl JS (1996) Potassium channels, proliferation and G1 progression. J Membr Biol 154(2):91–107. doi:10.1007/s002329900135 PubMedCrossRefGoogle Scholar
  4. 4.
    Schwab A (2001) Function and spatial distribution of ion channels and transporters in cell migration. Am J Physiol Renal Physiol 280(5):F739–F747PubMedGoogle Scholar
  5. 5.
    Pardo LA, del Camino D, Sanchez A, Alves F, Bruggemann A, Beckh S et al (1999) Oncogenic potential of EAG K(+) channels. EMBO J 18:5540–5547. doi:10.1093/emboj/18.20.5540 PubMedCrossRefGoogle Scholar
  6. 6.
    Meyer R, Heinemann SH (1998) Characterization of an eag-like potassium channel in human neuroblastoma cells. J Physiol 508(Pt 1):49–56PubMedGoogle Scholar
  7. 7.
    Gavrilova-Ruch O, Schonherr K, Gessner G, Schonherr R, Klapperstuck T, Wohlrab W et al (2002) Effects of imipramine on ion channels and proliferation of IGR1 melanoma cells. J Membr Biol 188:137–149. doi:10.1007/s00232-001-0181-3 PubMedCrossRefGoogle Scholar
  8. 8.
    Farias LM, Ocana DB, Diaz L, Larrea F, Avila-Chavez E, Cadena A et al (2004) Ether a go-go potassium channels as human cervical cancer markers. Cancer Res 64(19):6996–7001. doi:10.1158/0008-5472.CAN-04-1204 PubMedCrossRefGoogle Scholar
  9. 9.
    Hemmerlein B, Weseloh RM, de Queiroz FM, Knötgen H, Sánchez A, Rubio ME et al (2006) Overexpression of Eag1 potassium channels in clinical tumours. Mol Cancer 5:41. doi:10.1186/1476-4598-5-41 PubMedCrossRefGoogle Scholar
  10. 10.
    Pardo LA, del Camino D, Sanchez A, Alves F, Bruggemann A, Beckh S et al (1999) Oncogenic potential of EAG K(+) channels. EMBO J 18:5540–5547. doi:10.1093/emboj/18.20.5540 PubMedCrossRefGoogle Scholar
  11. 11.
    Ju M, Wray D (2002) Molecular identification and characterization of human EAG2 potassium channel. FEBS Lett 524(1–3):204–210. doi:10.1016/S0014-5793(02)03055-7 PubMedCrossRefGoogle Scholar
  12. 12.
    Abdul M, Hoosein N (2002) Voltage-gated potassium ion channels in colon cancer. Oncol Rep 9(5):961–964PubMedGoogle Scholar
  13. 13.
    Abdul M, Hoosein N (2002) Expression and activity of potassium ion channels in human prostate cancer. Cancer Lett 186(1):99–105. doi:10.1016/S0304-3835(02)00348-8 PubMedCrossRefGoogle Scholar
  14. 14.
    Cherubini A, Taddei GL, Crociani O, Paglierani M, Buccoliero AM, Fontana L et al (2000) HERG potassium channels are more frequently expressed in human endometrial cancer as compared to non-cancerous endometrium. Br J Cancer 83(12):1722–1729. doi:10.1054/bjoc.2000.1497 PubMedCrossRefGoogle Scholar
  15. 15.
    Bianchi L, Wible B, Arcangeli A, Taglialatela M, Morra F, Castaldo P et al (1998) Herg encodes a K+ current highly conserved in tumors of different histogenesis: a selective advantage for cancer cells? Cancer Res 58(4):815–822PubMedGoogle Scholar
  16. 16.
    Pillozzi S, Brizzi MF, Balzi M, Crociano O, Cherubini A, Guasti L et al (2002) HERG potassium channels are constitutively expressed in primary human acute myeloid leukemias and regulate proliferation of normal and leukemic hematopoietic progenitors. Leukemia 16(9):1791–1798. doi:10.1038/sj.leu.2402572 PubMedCrossRefGoogle Scholar
  17. 17.
    Cayabyab FS, Schlichter LC (2002) Regulation of an ERG. J Biol Chem 277(16):13673–13681. doi:10.1074/jbc.M108211200 PubMedCrossRefGoogle Scholar
  18. 18.
    Wang H, Zhang Y, Cao L, Han H, Wang J, Yang B et al (2002) HERG K+ channel, a regulator of tumor cell apoptosis and proliferation. Cancer Res 62(17):4843–4848PubMedGoogle Scholar
  19. 19.
    Chen S, Jiang M, Zhen Y (2005) HERG K+ channel expression-related chemosensitivity in cancer cells and its modulation by erythromycin. Cancer Chemother Pharmacol 56:212–220. doi:10.1007/s00280-004-0960-5 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, B.V. 2008

Authors and Affiliations

  • Surbhi Wadhwa
    • 1
  • Pankaj Wadhwa
    • 2
    • 3
  • Amit K. Dinda
    • 4
  • Narmada P. Gupta
    • 3
  1. 1.Department of AnatomyAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.Department of UrologySt Stephen’s HospitalNew DelhiIndia
  3. 3.Department of UrologyAll India Institute of Medical SciencesNew DelhiIndia
  4. 4.Department of PathologyAll India Institute of Medical SciencesNew DelhiIndia

Personalised recommendations