INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA BY THE ANTIESTROGENS DROLOXIFENE, TAMOXIFEN, AND TOREMIFENE IN MCF-7 CELLS
INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA BY THE ANTIESTROGENS DROLOXIFENE, TAMOXIFEN, AND TOREMIFENE IN MCF-7 CELLS
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DOI：
10.1097/00000421-199112002-00005
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发表时间：
1991-01-01
影响因子：
2.6
通讯作者：
DICKSON, RB
中科院分区：
文献类型：
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作者：
KNABBE, C;ZUGMAIER, G;DICKSON, RB
我们先前已经证明转化生长因子-β(转化生长因子-β)是雌激素反应性人乳腺癌细胞MCF-7中一种受激素调节的负生长因子。我们现在比较了抗雌激素他莫昔芬、屈洛昔芬(3-羟基他莫昔芬)和托瑞米芬诱导MCF-7细胞分泌自身抑制的转化生长因子-β的能力。主要结果如下：屈洛昔芬诱导的转化生长因子-β的分泌比相同浓度的他莫昔芬或托瑞米芬高2~3倍。他莫昔芬或托瑞米芬的浓度是屈洛昔芬的5-10倍，才能达到类似的转化生长因子-β分泌诱导作用。与他莫昔芬相比，间歇应用屈洛昔芬在诱导转化生长因子-β的分泌方面与持续治疗同样有效。根据这些数据，我们得出结论，转化生长因子-β蛋白是抗雌激素作用的标志物，也可能在其作用机制中发挥关键作用。在体外，屈洛昔芬是一种比他莫昔芬和托瑞米芬更有效的转化生长因子-β诱导剂和雌激素反应性人乳腺癌细胞的生长抑制因子。因此，屈洛昔芬在治疗乳腺癌方面也可能具有较高的抗雌激素潜能。
We have previously shown that transforming growth factor-beta (TGF-beta) is a hormonally regulated negative growth factor in estrogen responsive MCF-7 human breast cancer cells. We have now compared the antiestrogens tamoxifen, droloxifene (3-hydroxytamoxifen), and toremifene in their ability to induce the secretion of autoinhibitory TGF-beta by MCF-7 cells. The main results are as follows: induction of TGF-beta secretion by droloxifene is about two to three times higher than by identical concentrations of tamoxifen or toremifene. A 5-10 times higher concentration of tamoxifen or toremifene than droloxifene is necessary to reach a similar induction of TGF-beta secretion. In contrast to tamoxifen, intermittent application of droloxifene is as effective as continuous treatment in inducing TGF-beta secretion. We conclude from these data that TGF-beta proteins represent markers of antiestrogen action and might also play a pivotal role in their mechanism of action. Droloxifene is a more effective inducer of TGF-beta and a more potent growth inhibitor for estrogen responsive human breast cancer cells than tamoxifen and toremifene in vitro. Therefore, droloxifene might also possess a higher antiestrogenic potential in treatment of human breast cancer.