Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 P154


1Medical University of Vienna, Department of Medicine III, Vienna, Austria; 2Medical University of Vienna, Department of Medical and Chemical Laboratory diagnostics, Vienna, Austria; 3Medical University of Vienna, Department of Endocrine Surgery, Vienna, Austria; 4University of Copenhagen, Department of Medical Biochemistry and Genetics, Copenhagen, Denmark; 5Medical University of Vienna, Department of Medicine I, Vienna, Austria.

Insulinomas are thought to be the result of reduced ß-cell death and hyperproliferation of this specific and highly differentiated cell type. Specific growth- factors are responsible for inducing ß- cell replication and might therefore be involved in insulinoma formation. Pluripotent islet progenitor cells are thought to be located at pancreatic ducts, which can give rise to novel islets as well as exocrine pancreas formation. TGFß1 signalling disruption has been shown to result in premalignant ductal lesions in mouse models as well as in humans.

The specific objective of this study was to evaluate the gene expression profile of human insulinoma tumors compared with human islets. The gene expression profile of three human insulinomas originating from different individuals was compared to one islet donor. The comparative Affimetrix gene chip analysis of 8000 spotted genes revealed 1102 upregulated (>1.5x) and 210 downregulated (>1.5x) genes. The results revealed significant differences in the expression of members of the TGFß signalling pathway. Insulinomas contained reduced TGFß1 and TGFß-induced proteins, but overexpressed TGFß receptors. These data were confirmed by quantitative real-time PCR expanding the numbers of insulinomas to 7 and islets-donors to 3. Our results suggest a novel important function of TGFß in development of human insulinomas and cell growth regulation at the islet of Langerhans. Furthermore they are in accordance with earlier data on the exocrine counterpart, where impairment of TGFß signalling is documented in ductal progenitor cells and premalignant ductal lesions leading to pancreatic adenocarcinomas. Apparently, in the presence of aberrant TGFß signalling, these unique pluripotent progenitor cells might be able to give rise to both endocrine and exocrine neoplasias.

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