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DNA repair and recombination factor Rad51 is over-expressed in human pancreatic adenocarcinoma

Oncogene volume 19, pages 2791–2795 (2000)Cite this article

Abstract

Molecular processes that could contribute to differences in chemo- and radioresistance include variations in DNA repair mechanisms. In mammalian cells, the product of the rad51 gene mediates DNA repair via homologous recombination. We describe that in contrast to conventional monolayer cell systems Rad51 protein accumulates to high-levels in three-dimensional cell culture models as well as in orthotopic xeno-transplants of human pancreatic cancer cells. Strikingly, over-expression of wild-type Rad51 was also found in 66% of human pancreatic adenocarcinoma tissue specimens. Functional analysis revealed that Rad51 over-expression enhances survival of cells after induction of DNA double strand breaks. These data suggest that perturbations of Rad51 expression contribute to the malignant phenotype of pancreatic cancer.

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Acknowledgements

We thank Maike Pacena for her technical assistance in preparing the tumour slides. mRNA samples were kindly provided by PD Dr Hartmut Juhl and Dr Yuan Gao, orthotopic tumours of SCID mice were provided by Dr Alexander Fiedler, Clinic of General Surgery and Thoracic Surgery, Christian-Albrechts-University, Kiel. Calicheamicin γ1 was a gift by Wyeth-Ayerst Research, Pearl River, NY, USA. This work was supported by Deutsche Krebshilfe/Dr Mildred Scheel Stiftung (10-0944-St I, II) and Wilhelm-Sander Stiftung (97.020.01). H Kalthoff was supported by a grant given by the Medical Faculty of the University of Kiel (IZKF). The work is part of the MD theses of K Jost and S Opitz.

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Authors and Affiliations

  1. Institute for Human Genetics, Medical University, Ratzeburger Allee 160, Lübeck, D-23538, Germany

    H Maacke, K Jost, S Opitz, S Miska, Y Yuan, L Hasselbach & H-W Stürzbecher

  2. Institute for Pathology, Clinic for General and Thoracic Surgery, Christian-Albrechts-University, Michaelisstraße 5, Kiel, D-24105, Germany

    J Lüttges

  3. Molecular Oncology, Clinic for General and Thoracic Surgery, Christian-Albrechts-University, Michaelisstraße 5, Kiel, D-24105, Germany

    H Kalthoff

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  1. H Maacke
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  9. H-W Stürzbecher
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Maacke, H., Jost, K., Opitz, S. et al. DNA repair and recombination factor Rad51 is over-expressed in human pancreatic adenocarcinoma. Oncogene 19, 2791–2795 (2000). https://doi.org/10.1038/sj.onc.1203578

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