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PKCμ prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells

Oncogene volume 22, pages 8939–8947 (2003)Cite this article

Abstract

Loss of growth control and a marked resistance to apoptosis are considered major mechanisms driving tumour progression. Protein kinases C (PKC) have been shown to be important in the regulation of proliferation and apoptosis. In this report, we investigated the role of the PKC-like kinase PKCμ in the control of these processes in pancreatic adenocarcinoma cells. We demonstrate that in these cells, PKCμ expression strongly correlates with resistance to CD95-induced apoptosis. Inhibition of PKCμ with Goe6983 sensitized resistant cells to CD95-induced apoptosis. In CD95-sensitive Colo357 cells, forced overexpression of PKCμ strongly reduced CD95-mediated apoptosis, an effect that could be reversed by pretreatment with Goe6983. In addition, PKCμ overexpression led to a strongly enhanced cell growth and to a significant increase of telomerase activity. In an attempt to identify the signalling pathways affected by PKCμ, we identified the antiapoptotic proteins c-FLIPL and survivin to be strongly upregulated in PKCμ overexpressing cells. Immunohistochemical analysis of pancreatic tumour tissue of 48 patients and 10 normal pancreatic tissues revealed marked overexpression of PKCμ in tumours. In conclusion, we showed that PKCμ controls proliferative, as well as anti-apoptotic, signalling pathways and therefore plays an important role in acquiring the malignant phenotype of pancreatic tumours.

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Acknowledgements

We thank Angelika Duttmann for excellent technical assistance. Some of the data are part of the doctoral thesis of SS. This work was supported by the DFG (SFB415/Project A3).

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Authors and Affiliations

  1. Molecular Oncology, Clinic for General Surgery and Thoracic Surgery, Christian-Albrechts-University, Arnold-Heller-Str.7, Kiel, D-24105, Germany

    Anna Trauzold, Stefan Schmiedel, Hendrik Wermann, Sabine Westphal, Christian Röder, Lasse Lehnert, Hendrik Ungefroren & Holger Kalthoff

  2. Institute of Pathology, Christian-Albrechts-University, Kiel, 24105, Germany

    Bence Sipos

  3. Institute of Hematopathology and Lymph Node Registry, Christian-Albrechts-University, Kiel, 24105, Germany

    Wolfram Klapper

  4. 1st Department of Medicine, Laboratory of Molecular Gastroenterology, Christian-Albrechts-University, Kiel, 24105, Germany

    Alexander Arlt

  5. Fraunhofer Institute for Interfacial Engineering, Stuttgart, 70569, Germany

    Franz-Josef Johannes

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  1. Anna Trauzold
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Correspondence to Holger Kalthoff.

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Trauzold, A., Schmiedel, S., Sipos, B. et al. PKCμ prevents CD95-mediated apoptosis and enhances proliferation in pancreatic tumour cells. Oncogene 22, 8939–8947 (2003). https://doi.org/10.1038/sj.onc.1207001

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