Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatonin.
Differential responsiveness of MCF-7 human breast cancer cell line stocks to the pineal hormone, melatonin.
复制标题
MCF-7 人乳腺癌细胞系对松果体激素、褪黑激素的不同反应。
DOI：
10.1034/j.1600-079x.2000.280403.x
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发表时间：
2000
影响因子：
10.3
通讯作者：
Hill,SM
中科院分区：
文献类型：
--
作者：
Ram,PT;Yuan,L;Dai,J;Kiefer,T;Klotz,DM;Spriggs,LL;Hill,SM
雌激素受体（ER）阳性MCF-7人乳腺癌细胞系已广泛用于雌激素反应性人乳腺癌的研究。然而，在不同的MCF-7细胞储备中描述了不同水平的雌激素反应性。因为我们之前已经表明松果体激素褪黑激素抑制MCF-7细胞的增殖，并且可以调节ER表达和反式激活，所以我们研究了不同的MCF-7细胞储备是否对褪黑激素的抗增殖作用表现出不同的反应性以及可能的机制。检查MCF-7储备液（M、O、H）：（1）对雌二醇的促有丝分裂反应;（2）稳态ER mRNA水平;（3）mt 1褪黑激素膜受体的表达;（4）褪黑激素的生长抑制;（5）褪黑激素对ER和雌激素调节基因PgR、TGFβ和pS2表达的调节。对于所有这些参数，存在储液特异性响应，其显示：MCF-7 M>MCF-7 O>MCF-7 H。这些结果表明，各种MCF-7乳腺癌细胞对褪黑激素生长抑制作用的反应性存在显著差异，这可能与ER mRNA表达水平和雌激素反应性程度相关。这些发现表明，这些差异不仅可能对细胞的雌激素反应途径产生一些影响，而且褪黑激素的主要生长抑制作用通过膜相关G蛋白偶联的MT 1褪黑激素受体转导。
The estrogen receptor (ER)‐positive MCF‐7 human breast cancer cell line has been used extensively for the study of estrogen‐responsive human breast cancer. However, various levels of estrogen responsiveness have been described in different stocks of MCF‐7 cells. Because we have previously shown that the pineal hormone, melatonin, inhibits proliferation of MCF‐7 cells and can modulate ER expression and transactivation, we investigated if various stocks of MCF‐7 cells exhibit a differential responsiveness to the anti‐proliferative effects of melatonin and the possible mechanisms involved. The MCF‐7 stocks (M, O, H) were examined for: (1) mitogenic response to estradiol; (2) steady‐state ER mRNA levels; (3) expression of the mt1 melatonin membrane receptor; (4) growth inhibition by melatonin; and (5) melatonin's modulation of expression of the ER and the estrogen‐regulated genes, PgR, TGFβ and pS2. For all of these parameters, there was a stock‐specific response which showed: MCF‐7M>MCF‐7O>MCF‐7H. These results demonstrate that there are significant differences in the responsiveness of various stocks of MCF‐7 breast cancer cells to the growth‐inhibitory effects of melatonin which can be correlated with both the level of ER mRNA expression and the degree of estrogen‐responsiveness. These findings suggest that not only may these differences have some impact on the cells’ estrogen‐response pathway, but also that the primary growth‐inhibitory effects of melatonin are transduced through the membrane‐associated G‐protein coupled mt1 melatonin receptor.