Human breast cancer cell growth inhibition and deregulation of [Ca2+]i by estradiol.

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 p21waft/cip1. Such similarity together with the reported key role of intracellular ionized calcium [ca2+]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.