gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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The CK1delta/epsilon specific inhibitor IC261 abolishes the growth of pancreatic tumor cells and sensitizes pancreatic tumor cells against CD95-mediated apoptosis

Meeting Abstract

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  • corresponding author presenting/speaker Uwe Knippschild - Universitätsklinikum, Ulm, Deutschland
  • Benjamin Bohm - Universitätsklinikum Schleswig-Holstein, Kiel
  • Nadine Huber - Universitätsklinikum, Ulm
  • Georgios Giamas - Universitätsklinikum, Ulm
  • Thorsten Eismann - Universitätsklinikum, Ulm
  • Andreas Hillenbrand - Universitätsklinikum, Ulm
  • Doris Henne-Bruns - Universitätsklinikum, Ulm
  • Holger Kalthoff - Universitätsklinikum Schleswig-Holstein, Kiel
  • Anna Trauzold - Universitätsklinikum Schleswig-Holstein, Kiel
  • Claas Brockschmidt - Universitätsklinikum, Ulm

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO496

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk606.shtml

Published: March 20, 2006

© 2006 Knippschild et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Ductal adenocarcinoma of the pancreas show a specific pattern of genetic lesions and are characterized by genomic instability, invasiveness and rapid progression. Their profound resistance to chemotherapy is due to changes in signalling pathways controlling proliferation and cell death. Members of the CK1 kinase family, especially CK1 alpha, deltaand epsilon, are playing important regulatory roles in these pathways and have been shown to impede receptor mediated apoptosis on different levels. In the present study we show that CK1 delta and epsilon are constitutively expressed at higher protein levels in pancreatic tumor cells than CK1 alpha and that the well characterized CK1 delta/epsilon specific inhibitor IC261 (3-[(2,4,6-trimethoxyphenyl)methylidenyl]-indolin-2-one) abolishes the growth of all analyzed pancreatic tumor cell lines. IC261 treatment led preferently to an accumulation of cells in G2/M 24h after IC261 treatment. Interestingly, incubation of Panc89 cells with IC261 lead to a decreased expression of anti-apoptotic proteins like c-IAP1, c-IAP2, XIAP and BCL-xL and strongly sensitised these cells to CD95-mediated cell death. Similar results were obtained using another CK1 inhibitor CKI-7. Taken together, our results show that targeting CK1 isoforms, especially CK1 delta and epsilon, could provide a powerful strategy for the treatment of pancreatic tumors.