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.
Jain
P T
PT
Department of Pathology, School of Medicine, University of Maryland, Baltimore 21201, USA.
Trump
B F
BF
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018613:Microscopy, Confocal; D008938:Mitosis / Q000187:drug effects; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004958:Estradiol; D018844:Cyclin-Dependent Kinases; D002118:Calcium