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Exp Clin Endocrinol Diabetes 2007; 115(10): 674-682
DOI: 10.1055/s-2007-984477
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Reduced TGF-ß1 Expression and its Target Genes in Human Insulinomas

A. Nabokikh 1 , A. Ilhan 1 , M. Bilban 2 , W. Gartner 1 , G. Vila 1 , B. Niederle 3 , J. H. Nielsen 4 , O. Wagner 2 , W. Base 1 , A. Luger 1 , L. Wagner 1
  • 1Department of Medicine III, Medical University of Vienna
  • 2Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna and Ludwig Boltzmann Institute for Clinical and Experimental Oncology
  • 3Department of Endocrine Surgery, Medical University of Vienna
  • 4Department of Medical Biochemistry and Genetics, University of Copenhagen
Further Information

Publication History

received 21.03.2007 first decision 30.05.2007

accepted 22.06.2007

Publication Date:
30 November 2007 (online)

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Abstract

Aiming to identify signalling pathways relevant for ß-cell growth we performed an explorative micro-array analysis comparing the gene expression profiles of three human insulinomas and one normal pancreatic islet preparation. This revealed an insulinoma-associated down-regulation of the transforming growth factor beta 1 (TGF-ß1) and its target genes. Comparative quantitative real-time PCR (qRT-PCR) including an expanded sample number of both insulinomas (n=9) and pancreatic islet preparations (n=4) confirmed the decreased TGF-ß1 expression and its target molecules (TGFBI, NNMT, RPN2) in insulinomas. Similarly, TGF-ß1 immunofluorescense analysis revealed reduced expression in insulinomas when compared to pancreatic islets. In contrast, TGFBR2 (transforming growth factor beta receptor II) was found up-regulated. However, the consistent down-regulation of the TGF-ß1 targets TGFBI (transforming growth factor, beta-induced), NNMT (nicotinamide N-methyltransferase), RPN2 (ribophorin II) indicates that the parallel up-regulation of TGFBR2 does not compensate for the only marginal TGF-ß1 expression levels in insulinomas. TGFBR2 expression was confirmed at the protein level in insulinomas. SMAD2/3 protein expression was found at higher levels in human pancreatic islets when compared with insulinomas by dual colour confocal microscopy. TGF-ß1 signalling is known to be involved in cell replication and is abrogated in ductal pancreatic tumours. The down-regulation of TGF-ß1 expression and its target molecules in insulinomas is a new aspect of this cytokine. Our data underline parallels in endocrine and exocrine pancreatic tumour development, which may implicate common progenitor cells.

Key words

insulinoma - TGF-ß1 - islet of Langerhans

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Correspondence

L. WagnerMD 

Department of Medicine III

MUV

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Austria

Phone: +43/1/404 004 34 1

Fax: +43/1/404 007 79 0

Email: ludwig.wagner@meduniwien.ac.at

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