gms | German Medical Science

127. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

20.04. - 23.04.2010, Berlin

Sox9-associated overexpression of IFIT3 leads to pancreatic cancer progression by activation of "pseudoinflammatory" pathways

Meeting Abstract

  • Peter Camaj - Klinikum Großhadern, Exp. Forschung: Chirurgie, München, Deutschland
  • Ivan Ischenko - Klinikum Großhadern, Exp. Forschung: Chirurgie, München, Deutschland
  • Hendrik Seeliger - Klinikum Großhadern, Exp. Forschung: Chirurgie, München, Deutschland
  • Andrea Renner - Klinikum Großhadern, Exp. Forschung: Chirurgie, München, Deutschland
  • Karl-Walter Jauch - Universitätsklinikum der LMU München-Großhadern, Direktor der Chirurgischen Klinik und Poliklinik München Großhadern, München, Deutschland
  • Christiane J. Bruns - Universitätsklinikum der LMU, München-Großhadern, Chirurgische Klinik und Poliklinik, München, Deutschland

Deutsche Gesellschaft für Chirurgie. 127. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 20.-23.04.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10dgch093

DOI: 10.3205/10dgch093, URN: urn:nbn:de:0183-10dgch0935

Published: May 17, 2010

© 2010 Camaj et al.
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Outline

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Introduction: Inflammation plays important role in tumour initiation and progression. Here we report the role of the transcription factor Sox9 for regulation of IFIT3 an inflammation-related and tumour-promoting protein in pancreatic cancer.

Materials and methods: Low metastatic FG, high metastatic L3.6pl, and the stable transfected cell line FG-IFIT3 were used. To demonstrate effects on primary tumor growth and metastases in vivo we orthotopically injected the different cell lines in the pancreas of nude mice. To evaluate the VEGF depending angiogenic capacity of the different cell lines ELISA was used. By One STrEP technology we were able to identify IFIT3-binding partners. ChIP using anti-Sox9 antibody, followed by PCR amplifying the IFIT3-promoter was used to identify the interaction of the IFIT3P with the transcription factor Sox9.

Results: Analysis of differential gene expression demonstrated that the IFIT3 gene is up-regulated in L3.6pl cells as compared to FG cells. The Results clearly demonstrated tumor-promoting, pro-metastatic and pro-angiogenic features of IFIT3. One STrEP experiments identified JNK and STAT1 as binding partners of IFIT3. ChIP has demonstrated binding of the transcription factor Sox9 to the IFIT3 promoter. RT-PCR and immunoblot data demonstrated constitutive up-regulation of Sox9 expression in L3.6pl cells.

Conclusion: The inflammation associated protein IFIT3 is up-regulated in metastatic L3.6pl human pancreatic cancer cells and is in part responsible for the aggressive primary pancreatic tumor growth in vivo. Interestingly Sox9 binds to the IFIT3P and activates its expression. Since in L3.6pl cells Sox9 is constitutively overexpressed, IFIT3 is upregulated independent on the presence of the cytokine IFnα. Therefore, the proinflammatory IFnα-signaling pathway is activated even without actual inflammation in absence proinflammatory cytokine. The activation of such a “pseudo-inflammatory pathway” seems to be in part responsible for pancreatic cancer progression.