17-BETA-ESTRADIOL METABOLITES AFFECT SOME REGULATORS OF THE MCF-7 CELL-CYCLE

The activity of p34(cdc2) plays a key role in the regulation of the eu karyotic cell cycle. Another cell cycle associated molecule is PCNA. W e investigated the effects of 2-hydroxy-17 beta-estradiol, a cell prol iferator, and 2-methoxy-17 beta-estradiol, a potent inhibitor of cell growth, on the levels and activity of p34(cdc2) and on the levels of P CNA, as well as on protein phosphorylation in MCF-7 cells. 2-Hydroxyes tradiol increased p34(cdc2) activity at G(I)/S and elevated PCNA level s during S-phase. 2-Methoxyestradiol caused unscheduled activation of p34(cdc2) in S-phase and decreased levels of p34(cdc2) and PCNA during G(2)/M. We conclude that 2-hydroxy- and 2-methoxyestradiol have defin ite, though different regulatory functions during the cell cycle.