Aizu-Yokota E, Ichinoseki K, Sato Y
Kyoritsu College of Pharmacy, Tokyo, Japan.
Carcinogenesis. 1994 Sep;15(9):1875-9. doi: 10.1093/carcin/15.9.1875.
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.
采用抗β-微管蛋白抗体的间接免疫荧光法检测雌激素对细胞质微管网络的影响。天然存在的雌激素雌二醇可减少人乳腺癌细胞系MCF-7和MDA-MB-231间期细胞质微管纤维的数量。由于MDA-MB-231是雌激素受体阴性细胞系，雌二醇诱导的微管破坏似乎与雌二醇与受体的结合无关。在50%的细胞中诱导微管破坏所需的雌二醇有效浓度（EC50），MCF-7细胞为81微摩尔，MDA-MB-231细胞为82微摩尔。合成雌激素己烯雌酚也可诱导微管纤维减少，MCF-7细胞的EC50值为48微摩尔，MDA-MB-231细胞为50微摩尔。当用雌激素处理并使微管解聚的细胞被洗涤后，培养基换成新鲜的，细胞内微管网络在3小时内重新出现。当MCF-7细胞用雌二醇（50微摩尔）培养4天时，细胞生长被完全抑制。然而，雌酮对微管网络和细胞增殖的影响很小。这些结果表明，雌二醇诱导的微管破坏与其对细胞生长的抑制作用密切相关。
