CHANGES OF CELL CYCLE-REGULATING GENES IN INTERFERON-TREATED DAUDI CELLS

Interferon (IFN) modulates the expression of several genes and some of them are considered to be responsible for the inhibition of cellular growth. However, the alterations of cell cycle-regulating genes produc ed by IFN still remain unclear. Accordingly, we studied the expression of cell; cycle-regulating genes during IFN-induced growth arrest. Cel l cycle synchronized and unsynchronized Daudi Burkitt lymphoma cells w ere treated with IFN. Both the cell cycle distribution and the express ion of cell cycle-regulating genes (cdk2, cdc2, cyclins A, B, C, D3, c dc25, and wee1) were studied by flow cytometry and by Northern blot hy bridization or the reverse-transcription polymerase chain reaction, re spectively. Treated cells passed through the first G1 phase and gradua lly accumulated in the following G1 phase. Expression of cyclins A, B, and D3 oscillated along with the cell cycle progression in control ce lls, and the alterations of cyclin B expression were especially promin ent. Both cdc2 and cdk2 also showed changes, but these were not so dis tinct as observed with cyclin B. Expression of cdc25 and wee1 was litt le affected by cell cycle progression. In IFN-treated cells, expressio n of cyclins A and B were down-regulated, while that of cyclin C was n ot. Cyclin D3 expression was also down-regulated at 48 h, followed by an increase at 72 h. Expression of both cdc2 and cdk2 was down-regulat ed, especially that of the later. Wee1 expression was down-regulated b y IFN but, the expression of cdc25 remained stable. These findings sug gest that the modulation of cell cycle-regulating genes, particular by cyclin A and cdk2, plays an important role in IFN-induced cellular gr owth arrest.