SEQUENTIAL AND PROGRESSIVE CYCLIN EXPRESSION IN HUMAN OSTEOSARCOMA CELLS - DIAGNOSTIC AND THERAPEUTIC IMPLICATIONS

: Cyclin proteins in association with cyclin-dependent protein kinase (Cdk) subunits function to execute critical cell cycle transitions; dysregulation of these enzymes may play a pivotal role in human tumorigenesis. In this study we characterize the successive expression of cyclins D1, E, A, and B, as well as a novel cyclin-like protein, in synchronized human MG-63 osteosarcoma cells. The physiological activation, subunit configuration, and subcellular localization of cyclin D1 during the G1 phase of the cell cycle is characterized in additional detail. An essential role for cyclin D1 in osteosarcoma cell proliferation is inferred by the efficacy of an antisense oligo-deoxynucleotide strategy directed against this locus. In addition, we report on the amplification and comparative over-expression of cyclin D1 in a Ewing's sarcoma cell line. These findings support a sequential model of cyclin expression and suggest that examination of the levels of specific cyclins may provide valuable diagnostic and/or prognostic information in the evaluation of proliferative disorders.