Universität zu Köln

Mairinger, Fabian Dominik, Walter, Robert Fred Henry, Theegarten, Dirk, Hager, Thomas, Vollbrecht, Claudia ORCID: 0000-0002-0861-001X, Christoph, Daniel Christian, Worm, Karl, Ting, Saskia ORCID: 0000-0003-1415-7714, Werner, Robert, Stamatis, Georgios, Mairinger, Thomas, Baba, Hideo, Zarogoulidis, Konstantinos, Huang, Haidong, Li, Qiang, Tsakiridis, Kosmas, Zarogoulidis, Paul, Schmid, Kurt Werner and Wohlschlaeger, Jeremias (2014). Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours. J. Cancer, 5 (8). S. 646 - 655. LAKE HAVEN: IVYSPRING INT PUBL. ISSN 1837-9664

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Abstract

Background: Proteasomal subunit PSMB4 was suggested to be a survival gene in an animal model of hepatocellular carcinoma and in glioblastoma cell lines. In pulmonary adenocarcinoma, a high expression of these genes was found to be associated with poor differentiation and survival. This study investigates the gene expression levels of 26S proteasome subunits in human pulmonary neuroendocrine tumours including typical (TC) and atypical (AC) carcinoid tumours as well as small cell (SCLC) and large cell (LCNEC) neuroendocrine carcinomas. Material and methods: Gene expression levels of proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 neuroendocrine pulmonary tumours (each 20 TC, AC, LCNLC and SCLC) and compared to controls. mRNA levels were determined by using TaqMan assays. Immunohistochemistry on tissue microarrays (TMA) was performed to determine the expression of ki67, cleaved caspase 3 and PSMB4. Results: All proteasomal subunit gene expressions were significantly upregulated in TC, AC, SCLC and LCNEC compared to controls. PSMB4 mRNA is differently expressed between all neuroendocrine tumour subtypes demonstrating the highest expression and greatest range in LCNEC (p=0.043), and is significantly associated with proliferative activity (p=0.039). Conclusion: In line with other 26S proteasomal subunits PSMB4 is significantly increased, but differently expressed between pulmonary neuroendocrine tumours and is associated with the proliferative activity. Unlike in pulmonary adenocarcinomas, no association with biological behaviour was observed, suggesting that increased proteasomal subunit gene expression is a common and probably early event in the tumorigenesis of pulmonary neuroendocrine tumours regardless of their differentiation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mairinger, Fabian Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Robert Fred Henry UNSPECIFIED UNSPECIFIED UNSPECIFIED Theegarten, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Hager, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Vollbrecht, Claudia UNSPECIFIED orcid.org/0000-0002-0861-001X UNSPECIFIED Christoph, Daniel Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Worm, Karl UNSPECIFIED UNSPECIFIED UNSPECIFIED Ting, Saskia UNSPECIFIED orcid.org/0000-0003-1415-7714 UNSPECIFIED Werner, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamatis, Georgios UNSPECIFIED UNSPECIFIED UNSPECIFIED Mairinger, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Baba, Hideo UNSPECIFIED UNSPECIFIED UNSPECIFIED Zarogoulidis, Konstantinos UNSPECIFIED UNSPECIFIED UNSPECIFIED Huang, Haidong UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Qiang UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsakiridis, Kosmas UNSPECIFIED UNSPECIFIED UNSPECIFIED Zarogoulidis, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Kurt Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlschlaeger, Jeremias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-449336
DOI:	10.7150/jca.9955
Journal or Publication Title:	J. Cancer
Volume:	5
Number:	8
Page Range:	S. 646 - 655
Date:	2014
Publisher:	IVYSPRING INT PUBL
Place of Publication:	LAKE HAVEN
ISSN:	1837-9664
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER CELLS; MEDIATED DEGRADATION; PROTEIN-DEGRADATION; UBIQUITIN SYSTEM; BREAST-CANCER; KAPPA-B; PHASE-I; BORTEZOMIB; INHIBITOR; PATHWAY Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44933