Estradiol inhibits the growth of human breast cancer MCF-7 cells at supramicromolar concentrations. The mechanism of such phenomenon remains to be unravelled. Confocal laser scanning microscopic studies suggest elevation of [Ca2+](i) preceding bleb formation and cellular injury following acute and chronic treatment of ionomycin and estradiol at supramicromolar concentration. Phase contrast morphological study demonstrates metaphase-arrested cells and giant multinuclear cells possibly due to lack of cytokinesis caused by estradiol. There is a striking similarity between the morphological changes caused by estradiol and enforced overexpression of cyclin-dependent kinase inhibitor p21(waf1/clp1). Such similarity together with the reported key role of intracellular ionized calcium [ca(2+)](i) in regulating cyclin and deregulation of [Ca2+](i) by estradiol raises the possibility of deregulation of gene expression leading to inhibition of cyclin-dependent proliferative signals participating in inhibition of growth in MCF-7 cells.
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