Ist GIPC ein neuer Kandidat für die Therapie des Pankreaskarzinoms?

Translated title of the contribution: GIPC: a new target for therapy in pancreatic adenocarcinoma?

M. H. Muders, G. B. Baretton, D. E. Aust, S. K. Dutta, E. Wang, Y. Ikeda, M. R. Spaller, Kaustubh Datta, D. Mukhopadhyay

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

GIPC is highly expressed in human pancreatic adenocarcinoma and is a central protein for the stability of IGF-1R in pancreatic adenocarcinoma cell lines (15). The goal of this study was to prove the importance of GIPC in vivo and to evaluate possible therapeutic strategies that target this protein and its PDZ domain. In vivo effects of GIPC knockout were studied after lentiviral transduction of luciferase-expressing MiaPaCa2 pancreatic cancer cells with shRNA against GIPC; growth characteristics were monitored with bioluminiscence. Knockdown of GIPC led to a significant inhibition of pancreatic tumor cell growth in vivo in different mouse models. To test a possible therapeutic approach, the PDZ domain of GIPC was targeted by a short peptide composed of the amino acid sequence PSQSSSEA. This octapeptide was designed based on the C-terminal binding motif of GAIP. Targeting GIPC with this peptide inhibited the association between IGF-1R and GIPC. The subsequent downregulation of IGF-1R decreased proliferation in vitro and in vivo. In conclusion, our findings suggest that targeting GIPC and its PDZ domain-mediated interaction with the tyrosine kinase receptor IGF-1R could be a promising new treatment option for pancreatic cancer.

Original languageGerman
Pages (from-to)286-293
Number of pages8
JournalVerhandlungen der Deutschen Gesellschaft für Pathologie
Volume91
StatePublished - Jan 1 2007

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PDZ Domains
Adenocarcinoma
Pancreatic Neoplasms
Peptides
Protein Stability
Receptor Protein-Tyrosine Kinases
Growth
Luciferases
Small Interfering RNA
Amino Acid Sequence
Therapeutics
Down-Regulation
Cell Line
Neoplasms
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Muders, M. H., Baretton, G. B., Aust, D. E., Dutta, S. K., Wang, E., Ikeda, Y., ... Mukhopadhyay, D. (2007). Ist GIPC ein neuer Kandidat für die Therapie des Pankreaskarzinoms? Verhandlungen der Deutschen Gesellschaft für Pathologie, 91, 286-293.

Ist GIPC ein neuer Kandidat für die Therapie des Pankreaskarzinoms? / Muders, M. H.; Baretton, G. B.; Aust, D. E.; Dutta, S. K.; Wang, E.; Ikeda, Y.; Spaller, M. R.; Datta, Kaustubh; Mukhopadhyay, D.

In: Verhandlungen der Deutschen Gesellschaft für Pathologie, Vol. 91, 01.01.2007, p. 286-293.

Research output: Contribution to journalArticle

Muders, MH, Baretton, GB, Aust, DE, Dutta, SK, Wang, E, Ikeda, Y, Spaller, MR, Datta, K & Mukhopadhyay, D 2007, 'Ist GIPC ein neuer Kandidat für die Therapie des Pankreaskarzinoms?', Verhandlungen der Deutschen Gesellschaft für Pathologie, vol. 91, pp. 286-293.
Muders MH, Baretton GB, Aust DE, Dutta SK, Wang E, Ikeda Y et al. Ist GIPC ein neuer Kandidat für die Therapie des Pankreaskarzinoms? Verhandlungen der Deutschen Gesellschaft für Pathologie. 2007 Jan 1;91:286-293.
Muders, M. H. ; Baretton, G. B. ; Aust, D. E. ; Dutta, S. K. ; Wang, E. ; Ikeda, Y. ; Spaller, M. R. ; Datta, Kaustubh ; Mukhopadhyay, D. / Ist GIPC ein neuer Kandidat für die Therapie des Pankreaskarzinoms?. In: Verhandlungen der Deutschen Gesellschaft für Pathologie. 2007 ; Vol. 91. pp. 286-293.
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