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Immortalized bovine pancreatic duct cells become tumorigenic after transfection with mutant k-ras

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An Erratum to this article was published on 23 March 2012

Abstract

Mutation of the K-ras gene is thought to be an early and important event in pancreatic carcinogenesis. In order to study the role of this molecular alteration in the transition from the normal to the neoplastic pancreatic cell, bovine pancreatic duct cells were first immortalized by SV40 large T antigen (Ag) complementary (c)DNA transfection and then transfected with a mutated K-ras gene. As did primary duct cells, the immortalized duct cells (more than 100 passages) expressed cytokeratins, carbonic anhydrase type-II, cystic fibrosis transmembrane conductance regulator (CFTR), and multidrug resistance (mdr). They grew as a single layer after transplantation under plastic domes and formed three-dimensional structures resembling ducts when grown on Matrigel. Cell growth was stimulated by insulin, epidermal growth factor (EGF), transforming growth factor (TGF)-α, but cells did not respond to gastrin and CCK-8. They did not form colonies in soft agar nor did they form tumors in nude mice. Immortalized cells transfected with mutated K-ras acquired the ability to form tumors after orthotopic injection into the nude mouse pancreas. It is concluded that SV 40 immortalized bovine pancreatic duct cells retain the features of normal duct cells and gain tumorigenicity by transfection with mutated K-ras. This suggests an important role for K-ras in this pancreatic carcinoma model.

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Authors and Affiliations

  1. Department of Medicine IV, Molecular Gastroenterology, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Germany

    Matthias Löhr

  2. Department of Medicine, University of Rostock, Rostock, Germany

    Petra Müller, Christian Schmidt, Stefan Liebe & Ralf Jesnowski

  3. Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany

    Ira Zauner & Birgit Trautmann

  4. Department of Physiology, University of Saarland, Bad Homburg, Germany

    Frank Thévenod

  5. Laboratori d’Investigació Gastrointestinal, Institut de Recerca, Hospital de Sant Pau, Universita Autonoma, Barcelona, Spain

    Gabriel Capellα & Antonio Farré

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  1. Matthias Löhr
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  2. Petra Müller
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  3. Ira Zauner
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  4. Christian Schmidt
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Correspondence to Matthias Löhr.

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An erratum to this article is available at http://dx.doi.org/10.1007/s00428-012-1221-3.

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Löhr, M., Müller, P., Zauner, I. et al. Immortalized bovine pancreatic duct cells become tumorigenic after transfection with mutant k-ras. Virchows Arch 438, 581–590 (2001). https://doi.org/10.1007/s004280100397

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