17β-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 eukaryotic cell cycle. Another cell cycle associated molecule is PCNA. We investigated the effects of 2-hydroxy-17β-estradiol, a cell proliferator, and 2-methoxy-17β-estradiol, a potent inhibitor of cell growth, on the levels and activity of p34^cdc2 and on the levels of PCNA, as well as on protein phosphorylation in MCF-7 cells. 2-Hydroxyestradiol increased p34^cdc2 activity at G₁/S and elevated PCNA levels during S-phase. 2-Methoxyestradiol caused unscheduled activation of p34^cdc2 in S-phase and decreased levels of p34^cdc2 and PCNA during G₂/M. We conclude that 2-hydroxy- and 2-methoxyestradiol have definite, though different regulatory functions during the cell cycle.