Role of Cyclin B1/Cdc2 Up-Regulation in the Development of Mitotic Prometaphase Arrest in Human Breast Cancer Cells Treated with Nocodazole
Figure 7
Schematic explanation of the contribution of an early cyclin B1/Cdc2 up-regulation to the development of prometaphase arrest in cells treated with nocodazole.
Treatment of cancer cells with nocodazole causes microtubule disruption and thereby prevents microtubules from attaching to kinetochores in prometaphase cells. The unattached kinetochores will be bound by MAD2, which prevents the progression from prometaphase to metaphase and anaphase. It is speculated that the kinetochore-bound MAD2 protein plays an important role in mediating the up-regulation of cyclin B1 and Cdc2 proteins in prometaphase-arrested cells. The rapid increase of these two cell cycle proteins in prometaphase cells and particularly their accumulation in the nuclei are expected to be largely responsible for the development of characteristic nuclear phenotypes. Following a prolonged prometaphase arrest, the nocodazole-treated cells are expected to undergo cell death via intrinsic apoptosis pathways.