Universität zu Köln

Mairinger, Fabian D., Walter, Robert F. H., Ting, Saskia ORCID: 0000-0003-1415-7714, Vollbrecht, Claudia ORCID: 0000-0002-0861-001X, Kollmeier, Jens ORCID: 0000-0002-8048-3895, Griff, Sergei, Hager, Thomas, Mairinger, Thomas, Christoph, Daniel C., Theegarten, Dirk, Schmid, Kurt Werner and Wohlschlaeger, Jeremias (2014). Mdm2 protein expression is strongly associated with survival in malignant pleural mesothelioma. Future Oncol., 10 (6). S. 995 - 1006. LONDON: FUTURE MEDICINE LTD. ISSN 1744-8301

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Abstract

Aims:TP53 mutations are extremely rare in malignant pleural mesothelioma (MPM). In TP53 wild-type tumors, the functional p53 protein can be inactivated by MDM2. Materials & methods: A total of 61 patient samples were tested for their Mdm2 and p53 protein expression levels via immunohistochemistry. Results: This study demonstrates nuclear Mdm2 expression in three out of four mesothelioma cell lines and 21.3% of the MPM specimens investigated. After silencing of the MDM2 gene by siRNA in MPM cell lines, Mdm2 immunoexpression is lost and cells show changes indicative of severe damage. Mdm2 protein expression in MPM is detected in epithelioid and biphasic subtypes only and is significantly associated with poor survival compared with Mdm2-negative tumors. This may be explained by increased Mdm2 levels possibly leading to an increased ubiquitilation and proteasomal degradation of functional p53 protein. Conclusion: Expression of Mdm2 is a strong prognostic factor associated with shortened overall survival in MPM.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mairinger, Fabian D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Robert F. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ting, Saskia UNSPECIFIED orcid.org/0000-0003-1415-7714 UNSPECIFIED Vollbrecht, Claudia UNSPECIFIED orcid.org/0000-0002-0861-001X UNSPECIFIED Kollmeier, Jens UNSPECIFIED orcid.org/0000-0002-8048-3895 UNSPECIFIED Griff, Sergei UNSPECIFIED UNSPECIFIED UNSPECIFIED Hager, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Mairinger, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Christoph, Daniel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Theegarten, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Kurt Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlschlaeger, Jeremias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-438704
DOI:	10.2217/fon.13.261
Journal or Publication Title:	Future Oncol.
Volume:	10
Number:	6
Page Range:	S. 995 - 1006
Date:	2014
Publisher:	FUTURE MEDICINE LTD
Place of Publication:	LONDON
ISSN:	1744-8301
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SMALL-MOLECULE INHIBITORS; TUMOR-SUPPRESSOR GENE; P53 PATHWAY; IN-VIVO; EMBRYONIC LETHALITY; MUTATIONAL ANALYSIS; DOWN-REGULATION; UBIQUITINATION; MECHANISM; CANCER Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43870