Cell cycle analysis and expression of cell cycle regulator genes in myeloma cells overexpressing cyclin D1

Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression cause d by t(11;14)(q13;q32) is considered to be the most frequent in myeloma pat ients and cell lines, and may be a prognostic factor clinically. To elucida te the cellular biological role of overexpressed cyclin DI in myeloma cells , we examined the mRNA expression levels of cell cycle regulators including three cyclin Ds, cyclin-dependent kinase inhibitors (CDK-Is) and accelerat ors. Cyclin D1 overexpression was clearly demonstrated in the lines with ab normal 11q13 and associated with overexpression of S and G(2) accelerator g enes. The cyclin DI-overexpressing lines tended to have a shortened G(1) ph ase compared with the non-expressing lines. In addition, artificial silenci ng using antisense oligonucleotides for cyclin DI suppressed the growth rat e of some but not all cyclin DI-overexpressing cells. These results indicat e that overexpression of cyclin DI caused by cytogenetic abnormalities may make cells progress through the cell cycle rapidly, but it seems that other factors such as cyclin D2 and translocation-related genes affect the cell cycle progression in myeloma cells.