LASER-SCANNING CYTOMETRIC ANALYSIS OF CYCLIN B1 IN PRIMARY HUMAN MALIGNANCIES

Cyclins are key components of the cell cycle progression machinery. Th ey activate their partner-dependent kinases (CDKs) and target them to respective substrate proteins within the cell. CDK-mediated phosphoryl ation of specific sets of proteins drives the cell through particular phases or checkpoints of the cell cycle. During unperturbed growth of normal cells, the timing of expression of several cyclins is discontin uous, occurring at discrete and well-defined periods of the cell cycle . Immunocytochemical detection of cyclins in relation to cell cycle po sition (DNA content) by multiparameter now cytometric techniques has p rovided a new approach to cell cycle studies, This approach, Like no o ther, method, can be used to detect the ''unscheduled'' expression of cyclins, namely, the presentation of G(1) cyclins by cells in G(2)/M a nd of G(2)/M cyclins by G(1) cells, without the need for cell synchron ization. By use of multiparameter now cytometric and laser scanning cy tometric analysis, we correlated the expression of cyclin B1 with cell cycle position in normal lymphocytes stimulated to proliferate by the mitogen phytohemagglutinin and in 28 primary human tumors of differen t organ and type. Eighteen of the 28 tumors expressed the cyclin B1 in more than 5% of cells (B1 positive), and the rest showed cyclin expre ssion from 2.1 to 5% (B1 negative), In normal lymphocytes, the express ion of cyclin B1 was restricted to very late S and G(2) + M phases of the cell cycle. In 15 of 18 primary tumors studied, the expression of cyclin B1 was ''unscheduled'' (unrestricted to particular phases of th e cycle). The data suggest that the ''unscheduled'' expression of cycl in B1 might be a common defect in neoplasia.