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62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie

14. - 15.04.2016, Münster

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The Mediator complex subunit MED8 is implicated in the progression of renal cell carcinoma

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  • presenting/speaker I. Syring - Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany; Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • N. Klümper - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • Z. Shaikhibrahim - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • A. Offermann - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • M. Braun - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • M. Deng - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • D. Böhm - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • A. Queisser - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • A. von Mäßenhausen - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • J. Brägelmann - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany
  • J. Ellinger - Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany
  • S.C. Müller - Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany
  • S. Perner - Department of Prostate Cancer Research, Institute of Pathology, Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany; Pathology Network of the University Hospital of Luebeck and Leibniz Research Center Borstel, Luebeck, Germany

Nordrhein-Westfälische Gesellschaft für Urologie. 62. Kongress der Nordrhein-Westfälischen Gesellschaft für Urologie. Münster, 14.-15.04.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocV1.4

doi: 10.3205/16nrwgu13, urn:nbn:de:0183-16nrwgu138

Published: February 25, 2016

© 2016 Syring et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Introduction: The Mediator is an evolutionarily conserved complex and constitutes a regulator of gene transcription. The Mediator consists of 33 subunits (MEDs) and several studies demonstrated the involvement of the Mediator complex and altered expressions of particular subunits in diverse human diseases, especially in cancer. However a systematic study deciphering the transcriptional expression of the Mediator complex across cancer entities, including the urogenital tumors, was still lacking.

Material and methods: We performed an in depth in-silico-analysis obtained from the Oncomine database. We analyzed the mRNA expression of the Mediator in cancer vs. benign tissue (n=178,612) for 20 tumor entities. The data was validated at protein level for a subset of MEDs and cancer types, among others, MED8 in renal cell carcinoma (RCC). Immunohistochemical (IHC) staining against MED8 was performed on a tissue microarray (TMA) containing kidney cancer specimen [benign n=22, clear cell RCC (ccRCC) n= 143, papillary RCC (pRCC) n= 31]. We assessed the MED8 protein expression using the image analysis software Definiens® and SPSS V22 for statistics. Western blot was made for the screening of the RCC cell lines A498, ACHN, Caki2, and 769p for the expression of MED8. The knockdown of MED8 was done with siRNA. MTT proliferation and boyden chamber assays are running.

Results: The transcriptional expression profiles of the MEDs differed specific across the 20 tumor entities analyzed. For urogenital tumors, most strikingly, MED8 was found to be overexpressed in 20% of all RCC (10/50) with a mean fold change of 2. This overexpression was confirmed on protein level at a frequency of 21% (n=37/174) via IHC. Most pronounced, the pRCC samples showed significantly higher nuclear MED8 protein expression than benign tissue (71%, 22/31, p< 0.0001). In comparison, in ccRCC an overexpression of 10.5% was found (15/143, p< 0.0001). A first screening of the cell lines by western blotting showed an expression of MED8 and the knockdown of MED8 in the cell lines was established, thus the planned functional experiments by proliferation assay and migration assay will be workable.

Conclusion: MEDs exhibit cancer entity specific transcriptional expression profiles. Especially in RCC, MED8 seems to be have an crucial role in the development of pRCC. The functional analyses are running, the first results show the influence of the MED8 knockdown in proliferation and migration.