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Abstract A38: Maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer
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| Zeitschriftentitel: | Cancer Research |
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| Personen und Körperschaften: | , , , , , , , , , |
| In: | Cancer Research, 72, 2012, 4_Supplement, S. A38-A38 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>Loss of cell cycle control is a prerequisite for cancer onset and progression. In prostate cancer, increased activity of cell cycle proliferating 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.</jats:p> <jats:p>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 &lt; 0.05), which are associated with a severe disease course. Out of these, 15 genes are assigned to cell cycle process. The gene maternal embryonic leucine zipper kinase (MELK) was identified to be highly correlated with cell cycle and prostate cancer associated genes like UBE2C, TOP2A, CCNB2 and AURKB, and was therefore further included into validation and functional experiments. The association between MELK gene expression and high-risk prostate cancer was validated in an independent patient cohort (p &lt; 0.005, n = 79). Furthermore, our finding was supported by a public microarray dataset showing a higher MELK expression in prostate cancer patients with biochemical relapse. Immunohistochemical analysis using a tissue microarray (n = 94) revealed increased MELK protein expression in prostate cancer tissues of high Gleason scores. Knockdown of MELK decreased cell viability in PC3 and LNCaP cells. Microarray analysis upon MELK knockdown experiments revealed downstream processes like chromatin modification, embryonic development and cell migration. Our findings indicate that the protein serine/threonine kinase MELK represents a promising marker for advanced prostate cancer disease.</jats:p> <jats:p>Citation Format: Ruprecht Kuner, Holger Sültmann, Maria Fälth, Nicole Chui Pressinotti, Jan Christoph Brase, Sabrina Balaguer-Puig, Georg Schäfer, Georg Bartsch, Eberhard Steiner, Helmut Klocker. Maternal embryonic leucine zipper kinase (MELK) is upregulated in highgrade prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A38.</jats:p> |
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| Umfang: | A38-A38 |
| ISSN: |
1538-7445
0008-5472 |
| DOI: | 10.1158/1538-7445.prca2012-a38 |