World Journal of Urology

, Volume 29, Issue 6, pp 779–786

Alterations of the gene expression profile in renal cell carcinoma after treatment with the histone deacetylase-inhibitor valproic acid and interferon-alpha

  • E. Juengel
  • M. Bhasin
  • T. Libermann
  • S. Barth
  • M. Michaelis
  • J. CinatlJr
  • J. Jones
  • L. Hudak
  • D. Jonas
  • R. A. Blaheta
Original Article

Abstract

Purpose

Renal cell carcinoma (RCC) is highly resistant to chemotherapy and unresponsive to radio- and immunotherapy. Recently, we have documented that the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) in combination with low-dosed interferon (IFN)-alpha significantly inhibits RCC proliferation and adhesion in vitro and in vivo. The current study investigated the effects of these compounds on gene transcription of metastatic RCC cell line Caki-1 after 3 and 5 days exposure.

Methods

To evaluate the gene expression profiles of the RCC cells, we performed microarray analysis using Affymetrix GeneChip. Selected significant genes were further validated by Real Time PCR.

Results

Microarray revealed that VPA altered genes that are involved in cell growth, cell survival, immune response, cell motility and cell adhesion. Combination of VPA with IFN-alpha not only enhanced the effects on gene transcription but also resulted in the expression of novel genes, which were not induced by either VPA or IFN-alpha alone. Among the up-regulated genes were chemokines (CXCL10, CXCL11, CXCL16) and integrins (ITGA2, ITGA4, ITGA5, ITGA6, ITGA7). Genes encoding for adhesion molecules (NCAM1, ICAM1, VCAM1) were also modulated. Real Time PCR approved these findings.

Conclusion

This data provides insight into the molecular mechanism of action of the combined treatment of VPA and IFN-alpha in RCC. Implications are that the combined application of VPA and IFN-alpha may represent a more efficient alternative to existing therapy options for RCC.

Keywords

Renal cell carcinoma (RCC) HDAC inhibitor VPA Combination VPA + IFN Gene expression profiles 

Supplementary material

345_2010_582_MOESM1_ESM.pdf (36 kb)
Supplementary material 1 (PDF 36 kb)
345_2010_582_MOESM2_ESM.pdf (34 kb)
Supplementary material 2 (PDF 33 kb)
345_2010_582_MOESM3_ESM.pdf (49 kb)
Supplementary material 3 (PDF 48 kb)

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • E. Juengel
    • 1
  • M. Bhasin
    • 2
  • T. Libermann
    • 2
  • S. Barth
    • 3
  • M. Michaelis
    • 3
    • 4
  • J. CinatlJr
    • 4
  • J. Jones
    • 1
  • L. Hudak
    • 1
  • D. Jonas
    • 1
  • R. A. Blaheta
    • 1
  1. 1.Klinik für Urologie und Kinderurologie, Zentrum der Chirurgie, Klinikum der Johann Wolfgang Goethe-UniversitätInterdisziplinäres Forschungs- und Laborgebäude, Chirurgische ForschungFrankfurtGermany
  2. 2.Genomics Center, Beth Israel Deaconess Medical CenterHarvard Institutes of MedicineBostonUSA
  3. 3.blue-drugs GmbHFrankfurtGermany
  4. 4.Institut für Medizinische VirologieKlinikum der Johann Wolfgang Goethe-UniversitätFrankfurtGermany

Personalised recommendations