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Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells

Oncogene volume 24, pages 7964–7975 (2005)Cite this article

Abstract

The serine/threonine-specific casein kinase I delta (CKIδ) is ubiquitously expressed in all tissues, is p53 dependently induced in stress situations and plays an important role in various cellular processes. Our immunohistochemical analysis of the human placenta revealed strongest expression of CKIδ in extravillous trophoblast cells and in choriocarcinomas. Investigation of the functional role of CKIδ in an extravillous trophoblast hybrid cell line revealed that CKIδ was constitutively localized at the centrosomes and the mitotic spindle. Inhibition of CKIδ with the CKI-specific inhibitor IC261 led to structural alterations of the centrosomes, the formation of multipolar spindles, the inhibition of mitosis and, in contrast to other cell lines, the induction of apoptosis. Our findings indicate that CKIδ plays an important role in the mitotic progression and in the survival of cells of trophoblast origin. Therefore, IC261 could provide a new tool in treating choriocarcinomas.

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Abbreviations

CKIδ:

casein kinase I delta

DAPI:

4,6-diamidine-2-phenylindole hydrochloride

FCS:

fetal calf serum

mdm2:

mouse double minute 2

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Acknowledgements

We thank our colleague Dr Heukeshoven for the synthesis of the CKIδ-specific peptide 108. We also thank Solveig Aupers for technical advice on histological techniques, Dr Lars Behrend for his help in using the adenoviral p53 knockdown expression system and J Koppelmeyer for help with photographic work. Furthermore, we thank Professor Dr Günter Klöppel and PD Dr Peter Würl for helpful discussions and reading the manuscript. This work was supported by grants from the Deutsche Krebshilfe, Dr Mildred Scheel Stiftung, to Uwe Knippschild (10-1683-KN2 and 10-2237-KN3) and from the Deutsche Forschungsgemeinschaft to Hans-Georg Frank and Peter Kaufmann (Fr1245/3-3 and 4). The Heinrich Pette Institut is financially supported by Freie Hansestadt Hamburg and Bundesministerium für Gesundheit. This work is part of the PhD thesis of Martin Stöter, Fachbereich Biologie at the University of Hamburg.

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  1. Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

Authors and Affiliations

  1. Department of Visceral and Transplantation Surgery, University of Ulm, Ulm, Germany

    Martin Stöter, Doris Henne-Bruns & Uwe Knippschild

  2. Department of Gynecopathology, Institute of Pathology, University Hospital Eppendorf, Hamburg, Germany

    Ana-Maria Bamberger, Bilnaz Aslan & Thomas Löning

  3. The Heinrich Pette Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany

    Marion Kurth, Daniel Speidel, Jürgen Löhler & Wolfgang Deppert

  4. Department of Anatomy II, University of Technology, Aachen, Germany

    Hans-Georg Frank & Peter Kaufmann

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  1. Martin Stöter
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Stöter, M., Bamberger, AM., Aslan, B. et al. Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells. Oncogene 24, 7964–7975 (2005). https://doi.org/10.1038/sj.onc.1208941

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