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CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299

Oncogene volume 20, pages 590–598 (2001)Cite this article

Abstract

One of the major characteristics of anaplastic large cell lymphomas (ALCL) is the expression of the Ki-1/CD30 antigen. While the receptor mediates NF-κB-activation in Hodgkin's lymphomas, some data suggest the CD30-mediated apoptosis of other CD30-expressing cells. We were able to demonstrate that activation of CD30 leads to different effects regarding cell proliferation of the ALCL-derived cell lines Karpas 299 and JB6. Western and Northern blotting analysis revealed that CD30-induced growth inhibition of Karpas 299 cells correlated with a strong upregulation of the cell cycle inhibitor p21CIP1/WAF1. We found a non activating point mutation at codon 273 in exon 8 of the p53 gene in Karpas 299 cells which indicates an p53-independent mechanism for induced p21 expression. Abundant p21 protein expression resulted in hypophosphorylation of the retinoblastoma protein (Rb) and inhibition of the proliferating cell nuclear antigen (PCNA). CD30-stimulated cells showed no indications of apoptotic cell death, like genomic DNA fragmentation or cleavage of the caspase-3 target protein poly (ADP-ribose) polymerase (PARP). Our results indicate that CD30 is able to mediate an p21-associated cell cycle arrest in ALCL with possible implications for prognosis and clinical treatment.

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Acknowledgements

We would like to thank U Maurer, E Schneider and B Merk for helpful discussions and critical review of this manuscript. We also thank M Enz and D Stör for excellent technical assistance. This work was partially supported by a grant awarded by the Deutsche Krebshilfe (10-1406-Hü I).

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Authors and Affiliations

  1. Department of Internal Medicine III, University of Ulm, Germany

    Gabriele Hübinger, Elke Müller, Christof Schneider, Irmgard Sigg & Jochen Graf

  2. Department of Cellular and Molecular Biology, Karolinska Institute, Stockholm, Sweden

    Inka Scheffrahn & Bernhard B Singer

  3. Department of Molecular Biology, Robert-Koch-Institute, Berlin, Germany

    Eberhard Hildt

  4. Department of Internal Medicine III, Johann Wolfgang Goethe University, Frankfurt, Germany

    Lothar Bergmann

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  1. Gabriele Hübinger
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Hübinger, G., Müller, E., Scheffrahn, I. et al. CD30-mediated cell cycle arrest associated with induced expression of p21CIP1/WAF1 in the anaplastic large cell lymphoma cell line Karpas 299. Oncogene 20, 590–598 (2001). https://doi.org/10.1038/sj.onc.1204128

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