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

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 multi-polar 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. © 2005 Nature Publishing Group. All rights reserved.