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MED12 overexpressio...
MED12 overexpression is a frequent event in castration-resistant prostate cancer
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- Shaikhibrahim, Zaki (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Offermann, Anne (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Braun, Martin (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Menon, Roopika (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Syring, Isabella (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany; Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany
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- Nowak, Michael (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Halbach, Rebecca (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Vogel, Wenzel (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Ruiz, Christian (författare)
- Institute for Pathology, University Hospital Basel, Basel, Switzerland
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- Zellweger, Tobias (författare)
- Department of Urology, St. Claraspital, Basel, Switzerland
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- Rentsch, Cyrill A. (författare)
- Department of Urology, University Hospital Basel, Basel, Switzerland
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- Svensson, Maria, 1980- (författare)
- Region Örebro län,Department of Urology, Örebro University Hospital, Örebro, Sweden
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- Andrén, Ove, 1963- (författare)
- Region Örebro län,Örebro universitet, Institutionen för hälsovetenskap och medicin,Department of Urology, Örebro University Hospital, Örebro, Sweden
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- Bubendorf, Lukas (författare)
- Institute for Pathology, University Hospital Basel, Basel, Switzerland
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- Biskup, Saskia (författare)
- Center for Genomics and Transcriptomics, (CeGaT) GmbH, Tuebingen, Germany
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- Duensing, Stefan (författare)
- Section of Molecular Urooncology, Department of Urology, School of Medicine, University of Heidelberg, Heidelberg, Germany
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- Kirfel, Jutta (författare)
- Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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- Perner, Sven (författare)
- Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany
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(creator_code:org_t)
- Bioscientifica, 2014
- 2014
- Engelska.
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Ingår i: Endocrine-Related Cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 21:4, s. 663-675
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- In a recent effort to unravel the molecular basis of prostate cancer (PCa), Barbieri and colleagues using whole-exome sequencing identified a novel recurrently mutated gene, MED12, in 5.4% of primary PCa. MED12, encoding a subunit of the Mediator complex, is a transducer of Wnt/beta-catenin signaling, linked to modulation of hedgehog signaling and to the regulation of transforming growth factor beta (TGF beta)-receptor signaling. Therefore, these studies prompted us to investigate the relevance of MED12 in PCa. Expression of MED12, SMAD3 phosphorylation, and proliferation markers was assessed by immunohistochemistry on tissue microarrays from 633 patients. siRNA-mediated knockdown of MED12 was carried out on PCa cell lines followed by cellular proliferation assays, cell cycle analysis, apoptosis assays, and treatments with recombinant TGF beta 3. We found nuclear overexpression of MED12 in 40% (28/70) of distant metastatic castration-resistant prostate cancer (CRPCMET) and 21% (19/90) of local-recurrent CRPC (CRPCLOC) in comparison with frequencies of less than 11% in androgen-sensitive PCa, and no overexpression in benign prostatic tissues. MED12 expression was significantly correlated with high proliferative activity in PCa tissues, whereas knockdown of MED12 decreased proliferation, reduced G1-to S-phase transition, and increased the expression of the cell cycle inhibitor p27. TGF beta signaling activation associates with MED12 nuclear overexpression in tissues and results in a strong increase in MED12 nuclear expression in cell lines. Furthermore, MED12 knockdown reduced the expression of the TGF beta target gene vimentin. Our findings show that MED12 nuclear overexpression is a frequent event in CRPC in comparison with androgen-sensitive PCa and is directly implicated in TGF beta signaling.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- MED12
- overexpression
- prostate cancer
- castration-resistant
- Onkologi
- Oncology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Shaikhibrahim, Z ...
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Offermann, Anne
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Braun, Martin
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Menon, Roopika
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Syring, Isabella
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Nowak, Michael
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visa fler...
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Halbach, Rebecca
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Vogel, Wenzel
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Ruiz, Christian
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Zellweger, Tobia ...
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Rentsch, Cyrill ...
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Svensson, Maria, ...
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Andrén, Ove, 196 ...
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Bubendorf, Lukas
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Biskup, Saskia
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Duensing, Stefan
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Kirfel, Jutta
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Perner, Sven
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Endocrine-Relate ...
- Av lärosätet
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Örebro universitet