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

Cyclin proteins in association with cyclin-dependent protein kinase (C dk) subunits function to execute critical cell cycle transitions; dysr egulation of these enzymes may play a pivotal role in human tumorigene sis. In this study we characterize the successive expression of cyclin s D1, E, A, and B, as well as a novel cyclin-like protein, in synchron ized human MG-63 osteosarcoma cells. The physiological activation, sub unit configuration, and subcellular localization of cyclin D1 during t he G1 phase of the cell cycle is characterized in additional detail. A n essential role for cyclin D1 in osteosarcoma cell proliferation is i nferred by the efficacy of an antisense oligo-deoxynucleotide strategy directed against this locus. In addition, we report on the amplificat ion and comparative over-expression of cyclin D1 in a Ewing's sarcoma cell line. These findings support a sequential model of cyclin express ion and suggest that examination of the levels of specific cyclins may provide valuable diagnostic and/or prognostic information in the eval uation of proliferative disorders.