Diel Patrick, Olff Sabine, Schmidt Simone, Michna Horst
Institut für Morphologie und Tumorforschung, Deutsche Sporthochschule Köln, Carl-Diem-Weg 6, 50927, Köln, Germany
J Steroid Biochem Mol Biol. 2002 Jan;80(1):61-70. doi: 10.1016/s0960-0760(01)00173-x.
In the presented study, we have analysed effects of the environmental estrogens bisphenol A (BPA), p-tert-octylphenol (OCT), o,p'-DDT (DDT) and coumestrol (COU) on cell proliferation, apoptosis induction, progesterone receptor (PR) and androgen receptor (AR) mRNA expression and ER alpha protein expression in comparison to estradiol (E2) and the selective ER modulator (SERM) raloxifene (RAL) and the pure antiestrogen faslodex (ICI 182780) in the human breast cancer cell line MCF-7. A dose dependent analysis of the cell cycle distribution of MCF-7 cells after administration of OCT, DDT and COU revealed a significant induction of cell proliferation and reduced rate of apoptosis. Maximum induction of cell proliferation and the lowest rate of apoptosis could be observed at a dose of 10(-6)M. Interestingly, administration of BPA reduces the rate of apoptosis, but does not enhance proliferation at any dose analysed. PR mRNA expression in MCF-7 cells was up regulated after administration of COU and DDT, whereas treatment with BPA and OCT did not effect PR mRNA expression. AR mRNA expression was down regulated by COU, but not effected by BPA, DDT and OCT. The expression of ER alpha protein in the breast cancer cells was slightly down regulated by COU and DDT, but unaffected by BPA and OCT. In summary and in comparison to the effects observed after administration of E2, RAL and ICI our data indicate that none of the analysed compounds exhibit properties comparable to RAL and ICI. COU and DDT exhibit properties which are very similar to E2. Administration of BPA and OCT did not effect any of the estrogen sensitive molecular parameters analysed. Nevertheless OCT is a very potent stimulator of cell proliferation in MCF-7 cells. Surprisingly, BPA is not able to induce the proliferation of MCF-7 breast cancer cells, but turns out to be a very potent inhibitor of apoptosis. For this reason and in agreement to the effects of BPA on the molecular parameters analysed, we conclude that BPA does not act in a classical estrogen like manner in MCF-7 breast cancer cells.
在本研究中，我们分析了环境雌激素双酚A（BPA）、对叔辛基苯酚（OCT）、邻，对'-滴滴涕（DDT）和香豆雌酚（COU）与雌二醇（E2）、选择性雌激素受体调节剂（SERM）雷洛昔芬（RAL）以及纯抗雌激素氟维司群（ICI 182780）相比，对人乳腺癌细胞系MCF-7中细胞增殖、凋亡诱导、孕激素受体（PR）和雄激素受体（AR）mRNA表达以及雌激素受体α（ERα）蛋白表达的影响。对OCT、DDT和COU给药后MCF-7细胞的细胞周期分布进行剂量依赖性分析，结果显示细胞增殖显著诱导，凋亡率降低。在10⁻⁶M剂量下可观察到细胞增殖的最大诱导和最低凋亡率。有趣的是，BPA给药可降低凋亡率，但在任何分析剂量下均不增强增殖。COU和DDT给药后，MCF-7细胞中PR mRNA表达上调，而BPA和OCT处理对PR mRNA表达无影响。COU可下调AR mRNA表达，但BPA、DDT和OCT对其无影响。COU和DDT可使乳腺癌细胞中ERα蛋白表达略有下调，但BPA和OCT对其无影响。总之，与E2、RAL和ICI给药后观察到的效应相比，我们的数据表明，所分析的化合物均未表现出与RAL和ICI相当的特性。COU和DDT表现出与E2非常相似的特性。BPA和OCT给药对所分析的任何雌激素敏感分子参数均无影响。然而，OCT是MCF-7细胞中非常有效的细胞增殖刺激剂。令人惊讶的是，BPA不能诱导MCF-7乳腺癌细胞增殖，但却是非常有效的凋亡抑制剂。基于此，并与BPA对所分析分子参数的影响一致，我们得出结论，BPA在MCF-7乳腺癌细胞中并非以经典雌激素样方式起作用。
