Glucocorticoid inhibition of 235-1 rat pituitary tumor cell cycle progression.

Control of the cell cycle is accomplished by sequentially activated cyclin-dependent kinases and the action of inhibitory proteins. We have shown that exposure of 235-1 rat pituitary tumor cells to dexamethasone (DEX) leads to a 50% reduction in growth rate. We examined the mechanism by which DEX affects 235-1 cell proliferation by determining the expression levels of proteins involved in cell-cycle progression. The expression of the G1 markers c-Myc and cyclin D3 were unaffected by DEX treatment. Levels of retinoblastoma family proteins p107 and p116 Rb were not altered. The levels of p1 30/Rb2 were increased by DEX within 36 h of initiating treatment. Additionally, a higher-mobility Rb2-related protein appeared within 24 h and was further increased in DEX-treated cells by 36 h. We also observed reduced levels of M-phase proteins, Cdc2 kinase, and cyclin B in DEX-treated cells. These changes occurred prior to the reduction in cell numbers and thus may represent causative factors. Our data suggest that DEX induces a late G1 block in 235-1 cell-cycle passage, accompanied by a reduction in the levels of the regulatory proteins required for passage through subsequent phases of the cell cycle.