17beta-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-17beta-estradiol, a cell proliferator, and 2-methoxy-17beta-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.
Lottering
M L
ML
Department of Physiology, Faculty of Medicine, University of Pretoria, South Africa.
de Kock
M
M
Viljoen
T C
TC
Grobler
C J
CJ
Seegers
J C
JC
D016203:CDC2 Protein Kinase / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D016196:S Phase; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018809:Proliferating Cell Nuclear Antigen; D004958:Estradiol; D016203:CDC2 Protein Kinase