title: Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Fabian Dominik
authors.initials: FD
authors.lastname: Mairinger
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany. ; 2. Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Robert Fred Henry
authors.initials: RF
authors.lastname: Walter
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Theegarten
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hager
authors.affiliation: 3. Institute of Pathology, University Hospital Cologne, University of Cologne, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vollbrecht
authors.affiliation: 4. Department of Medical Oncology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Daniel Christian
authors.initials: DC
authors.lastname: Christoph
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Worm
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Ting
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Werner
authors.affiliation: 5. Department of Thoracic Surgery, Ruhrlandklinik, West German Lung Centre, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Stamatis
authors.affiliation: 6. Department of Pathology, Helios Klinikum Emil von Behring, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mairinger
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.affiliation: 7. Pulmonary-Oncology, ``G. Papanikolaou`` General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zarogoulidis
authors.affiliation: 8. Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Huang
authors.affiliation: 8. Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: 9. Thoracic Surgery Department, ``Saint Luke`` Private Clinic, Thessaloniki, Panorama, Greece.
authors.forename: Kosmas
authors.initials: K
authors.lastname: Tsakiridis
authors.affiliation: 7. Pulmonary-Oncology, ``G. Papanikolaou`` General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Paul
authors.initials: P
authors.lastname: Zarogoulidis
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Kurt Werner
authors.initials: KW
authors.lastname: Schmid
authors.affiliation: 1. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Germany.
authors.forename: Jeremias
authors.initials: J
authors.lastname: Wohlschlaeger
keywords: 26S Proteasome; TaqMan qPCR; carcinoid tumours; neuroendocrine lung carcinoma.; neuroendocrine lung tumours