1,25-dihydroxyvitamin D-3-induced retardation of the G(2)/M traverse is associated with decreased levels of p34(cdc2) in HL60 cells

Cellular differentiation of neoplastic cells after exposure to 1,25-dihydro xyvitamin D-3 (1,25 D-3) is accompanied by altered cell cycle regulation. I n previous studies, blocks in both G(1)/S and G(2)/M checkpoints have been observed in 1,25D(3)-treated HL60 cells, but the mechanism of the 1,25D(3)- induced G(2)/M block has not been previously reported. In this study, we sh ow by cell cycle analysis, using bromodeoxyuridine pulse-chase labeling, th at the G(2)/M block in 1,25D3-treated HL60 cells is incomplete. We also dem onstrate that although the 1,25D3-treated cells exhibit elevated levels of cyclin B1, Cdc25C, and Cdk7, which are positive regulators of the G(2)/M tr averse, these cells have decreased protein levels of p34(cdc2) and decrease d p34cdc2 kinase activity. This provides potential mechanisms for the obser ved accumulation of cells in the G(2) cell cycle compartment and occasional polyploidization following treatment of HL60 cells with 1,25D(3). The data also suggest that the ability of some cells to traverse this block may be the result of cellular compensatory mechanisms responding to decreased p34c dc2 activity by increasing the levels of other regulators of the G(2) trave rse, such as cyclin B1, Cdc25C, and Cdk7. J. Cell. Biochem. 75:226-234, 199 9. (C) 1999 Wiley-Liss, Inc.