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

Martin Stöter; Ana-Maria Bamberger; Bilnaz Aslan; Marion Kurth; Daniel Speidel; Thomas Löning; Hans-Georg Frank; Peter Kaufmann; Jürgen Löhler; Doris Henne-Bruns; Wolfgang Deppert; Uwe Knippschild

doi:10.1038/sj.onc.1208941

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

Oncogene. 2005 Dec 1;24(54):7964-75. doi: 10.1038/sj.onc.1208941.

Authors

Martin Stöter¹, Ana-Maria Bamberger, Bilnaz Aslan, Marion Kurth, Daniel Speidel, Thomas Löning, Hans-Georg Frank, Peter Kaufmann, Jürgen Löhler, Doris Henne-Bruns, Wolfgang Deppert, Uwe Knippschild

Affiliation

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

PMID: 16027726
DOI: 10.1038/sj.onc.1208941

Abstract

The serine/threonine-specific casein kinase I delta (CKIdelta) 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 CKIdelta in extravillous trophoblast cells and in choriocarcinomas. Investigation of the functional role of CKIdelta in an extravillous trophoblast hybrid cell line revealed that CKIdelta was constitutively localized at the centrosomes and the mitotic spindle. Inhibition of CKIdelta 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 CKIdelta 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.

MeSH terms

Apoptosis / drug effects*
Blotting, Western
Casein Kinase Idelta / antagonists & inhibitors*
Casein Kinase Idelta / genetics
Casein Kinase Idelta / metabolism
Cell Line
Cell Line, Transformed
Cell Survival / drug effects
Centrosome / drug effects
Choriocarcinoma / enzymology
Choriocarcinoma / metabolism
Choriocarcinoma / pathology
Female
Flow Cytometry
Genes, p53
Glutathione Transferase / metabolism
Green Fluorescent Proteins / metabolism
Histocytochemistry
Humans
Hybrid Cells / drug effects
Hybrid Cells / metabolism
Immunohistochemistry
Indoles / pharmacology*
Microscopy, Fluorescence
Phloroglucinol / analogs & derivatives*
Phloroglucinol / pharmacology
Placenta / cytology
Pregnancy
Protein Kinase Inhibitors / pharmacology
Recombinant Fusion Proteins / metabolism
Sequence Analysis, DNA
Spindle Apparatus / drug effects*
Trophoblasts / cytology*
Trophoblasts / drug effects*
Trophoblasts / enzymology
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

IC 261
Indoles
Protein Kinase Inhibitors
Recombinant Fusion Proteins
Tumor Suppressor Protein p53
Green Fluorescent Proteins
Phloroglucinol
Glutathione Transferase
Casein Kinase Idelta