Microtubule disruption induced by estradiol in estrogen receptor-positive and -negative human breast cancer cell lines.
Effects of estrogens on the cytoplasmic microtubule network were examined by the indirect immunofluorescence method using anti-beta-tubulin antibody. Estradiol, a naturally occurring estrogen, decreased the amount of cytoplasmic microtubule fibers during interphase in the human breast cancer cell lines MCF-7 and MDA-MB-231. Since MDA-MB-231 is an estrogen receptor-negative cell line, estradiol-induced microtubule disruption seems to be independent of estradiol binding to receptors. The effective concentration of estradiol required for induction of microtubule disruption in 50% of the cells (EC50) was 81 microM for MCF-7 cells and 82 microM for MDA-MB-231 cells. A synthetic estrogen, diethylstilbestrol, also induced a decrease in microtubule fibers, with an EC50 value of 48 microM for MCF-7 cells and 50 microM for MDA-MB-231 cells. When estrogen-treated and microtubule-depolymerized cells were washed and the medium was replaced with fresh, intracellular microtubule networks reappeared within 3 h. When MCF-7 cells were cultured for 4 days with estradiol (50 microM), cell growth was completely inhibited. However, estrone affected the microtubule network and cell proliferation only slightly. These results suggest that estradiol-induced microtubule disruption is closely related to its inhibitory effect on cell growth.
Aizu-Yokota
E
E
Kyoritsu College of Pharmacy, Tokyo, Japan.
Ichinoseki
K
K
Sato
Y
Y
D001943:Breast Neoplasms / Q000737:chemistry / Q000648:ultrastructure*; D002462:Cell Membrane / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure*; D011960:Receptors, Estrogen / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011960:Receptors, Estrogen; D004958:Estradiol; D004054:Diethylstilbestrol