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Journal of Molecular Medicine

, Volume 91, Issue 2, pp 237–248 | Cite as

The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer

  • Ruprecht Kuner
  • Maria Fälth
  • Nicole Chui Pressinotti
  • Jan C. Brase
  • Sabrina Balaguer Puig
  • Jennifer Metzger
  • Stephan Gade
  • Georg Schäfer
  • Georg Bartsch
  • Eberhard Steiner
  • Helmut Klocker
  • Holger Sültmann
Original Article

Abstract

Loss of cell cycle control is a prerequisite for cancer onset and progression. In prostate cancer, increased activity of cell cycle genes has been associated with prognostic parameters such as biochemical relapse and survival. The identification of novel oncogenic and druggable targets in patient subgroups with poor prognosis may help to develop targeted therapy approaches. We analyzed prostate cancer and corresponding benign tissues (n = 98) using microarrays. The comparison of high- and low-grade tumors (Gleason score ≥ 4 + 3 vs. ≤ 3 + 4) revealed 144 differentially expressed genes (p < 0.05). Out of these, 15 genes were involved in the cell cycle process. The gene maternal embryonic leucine zipper kinase (MELK) was identified to be highly correlated with cell cycle genes like UBE2C, TOP2A, CCNB2, and AURKB. Increased MELK gene expression in high-risk prostate cancer was validated by qPCR in an independent patient cohort (p < 0.005, n = 79). Immunohistochemistry analysis using a tissue microarray (n = 94) revealed increased MELK protein expression in prostate cancer tissues of high Gleason scores. RNAi-based inhibition of MELK in PC3 and LNCaP cells suggested putative function in chromatin modification, embryonic development and cell migration. The concerted inhibition of MELK and other cell cycle targets by the antibiotic siomycin A strongly impaired cell viability of prostate cancer cells, and may point to a novel therapy approach for a subset of high-risk prostate cancer patients.

Keywords

Prostate cancer Gleason score Microarray MELK Siomycin A 

Notes

Acknowledgments

We thank Denise Keitel, Marcello Schifani, Christof Seifarth, Birgit Stenzel, and Irma Sottsas for excellent technical assistance. We thank the DKFZ core facility for the microarray service. This study was supported by a grant of the Austrian Nationalstiftung and the Austria Wirtschaftsservice GmbH in the framework of the IMGuS research program (Institute for Medical Genome Research and Systems Biology, Wien).

Disclosure statement

The authors declare no conflict of interest.

Supplementary material

109_2012_949_MOESM1_ESM.pdf (196 kb)
ESM 1 (PDF 195 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ruprecht Kuner
    • 1
  • Maria Fälth
    • 1
    • 2
  • Nicole Chui Pressinotti
    • 1
    • 3
  • Jan C. Brase
    • 1
    • 4
  • Sabrina Balaguer Puig
    • 1
  • Jennifer Metzger
    • 1
  • Stephan Gade
    • 1
  • Georg Schäfer
    • 5
    • 6
  • Georg Bartsch
    • 5
  • Eberhard Steiner
    • 5
  • Helmut Klocker
    • 5
  • Holger Sültmann
    • 1
  1. 1.Unit Cancer Genome Research, Division of Molecular GeneticsGerman Cancer Research Center and National Center of Tumor DiseasesHeidelbergGermany
  2. 2.Cellzome AGHeidelbergGermany
  3. 3.Abbott GmbH and Co.KGWiesbadenGermany
  4. 4.Sividon Diagnostics GmbHCologneGermany
  5. 5.Department of UrologyInnsbruck Medical UniversityInnsbruckAustria
  6. 6.Institute for PathologyInnsbruck Medical UniversityInnsbruckAustria

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