Estradiol induces functional inactivation of p53 by intracellular redistribution

Estrogen treatment of MCF-7 cells grown in serum-free medium induced a modi fication of the intracellular distribution of p53 protein. Western blot ana lysis and immunofluorescence staining showed ed that p53 was localized in t he nucleus of untreated cell and that after 48 h of hormone treatment, it w as mostly localized in the cytoplasm. This effect was blocked by the anties trogen ICI182,780. Intracellular redistribution of p53 was correlated to a reduced expression of the WAF1/CIP1 gene product and to the presence of deg radation fragments of p53 in the cytosol. Estradiol treatment prevented the growth inhibition induced by oligonucleotide transfection, simulating DNA damage. This observation indicated that the wild-type p53 gene product pres ent in the MCF-7 cell could be inactivated bg estradiol through nuclear exc lusion to permit the cyclin-dependent phosphorylation events leading to the G(1)-S transition. In addition, the estradiol-induced inactivation of p53 could be involved in the tumorigenesis of estrogen-dependent neoplasm.