Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells.
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.
Stöter
Martin
M
Department of Visceral and Transplantation Surgery, University of Ulm, Ulm, Germany.
Bamberger
Ana-Maria
AM
Aslan
Bilnaz
B
Kurth
Marion
M
Speidel
Daniel
D
Löning
Thomas
T
Frank
Hans-Georg
HG
Kaufmann
Peter
P
Löhler
Jürgen
J
Henne-Bruns
Doris
D
Deppert
Wolfgang
W
Knippschild
Uwe
U
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D048148:Casein Kinase Idelta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects; D002822:Choriocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D016158:Genes, p53; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D008941:Spindle Apparatus / Q000187:drug effects*; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C411652:IC 261; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins; D010696:Phloroglucinol; D005982:Glutathione Transferase; D048148:Casein Kinase Idelta