gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Sonic Hedgehog(SHH) in pancreatic cancer: Effect of the small molecule inhibitor Hh-Antag

Meeting Abstract

  • corresponding author presenting/speaker Marcus Bahra - Klinik für Allgemein-, Visceral und Transplantationschirurgie, Charité, Berlin, Deutschland
  • Arend Koch - Institut für Neuropathologie, Universitätsklinikum, Bonn
  • Jan Michael Langrehr - Klinik für Allgemein-, Visceral und Transplantationschirurgie, Charité, Berlin
  • Wolfgang Hartmann - Institut für Neuropathologie, Universitätsklinikum, Bonn
  • Ulrich Schüller - Institut für Neuropathologie, Universitätsklinikum, Bonn
  • Nicole Schulz - Institut für Neuropathologie, Universitätsklinikum, Bonn
  • Peter Neuhaus - Klinik für Allgemein-, Visceral und Transplantationschirurgie, Charité, Berlin
  • Thorsten Pietsch - Institut für Neuropathologie, Universitätsklinikum, Bonn

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO131

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk241.shtml

Published: March 20, 2006

© 2006 Bahra et al.
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Outline

Text

Activation of the hedgehog signal transduction pathway, triggered by hedgehog binding to the transmembrane receptor PTCH or by mutations in the PTCH gene, plays an important role in the development of various tumors including cutaneous basal cell carcinomas and cerebellar medulloblastomas. Recent findings indicate that digestive tract tumors including pancreatic adenocarcinomas also display increased hedgehog signaling activity due to an abnormal expression of the secreted hedgehog ligand sonic hedgehog (Shh). To investigate if alterations of PTCH may also be involved in the pathogenesis of pancreatic adenocarcinomas we screened 38 tumors and 3 cell lines for mutations using single-strand conformation polymorphism analysis (SSCP) of all coding exons and direct sequencing. Furthermore, the expression levels of known hedgehog target genes were determined using the competitive RT-PCR method. A total of 26 pancreatic adenocarcinoma biopsies and 3 pancreatic cancer cell lines as well as constitutional normal pancreatic tissue were analyzed. In the majority of pancreatic cancers we found significant overexpression of the target genes GLI-1 and PTCH compared to the corresponding normal pancreatic tissue. Additionally the effects of the small molecule inhibitor of the Hedgehog-Patched pathway Hh-Antag (G-024856; CUR) were investigated. Hh-Antag inhibits the function of Smoothened in pancreatic cancer cells; this results in inhibition of cell proliferation.