Cappelletti Vera, Miodini Patrizia, Di Fronzo Giovanni, Daidone Maria Grazia
Department of Experimental Oncology, Unit #10, Istituto Nazionale Tumori, I-20133 Milan, Italy.
Int J Oncol. 2006 May;28(5):1185-91.
High consumption of phytoestrogen-rich food correlates with reduced incidence of breast cancer. However, the effect of phytoestrogens on growth of pre-existing breast tumors presents concerns when planning the use of phytoestrogens as chemoprevention st rategy. Genistein, the active phytoestrogen in soy, displays weak estrogenic activity mediated by estrogen receptor (ER) with a preferential binding for the ER-beta species. However, no information is at present available on the interaction between phytoestrogens and the various isoforms generated by alternative splicing. In two human breast cancer cell lines, T47D and BT20, which express variable levels of ER-beta, the effect of genistein and quercetin was evaluated singly and in comparison with 17beta-estradiol, on mRNA expression of estrogen receptor-beta (ER-beta) isoforms evaluated by a triple primer RT-PCR assay. In T47D cells estradiol caused a 6-fold up-regulation of total ER-beta, and modified the relative expression pattern of the various isoforms, up-regulating the beta2 and down-regulating the beta5 isoform. Genistein up-regulated ER-beta2 and ER-beta1 in T47D cells, and after treatment the ER-beta2 isoform became prevalent, while in BT20 cells it almost doubled the percent contribution of ER-beta1 and ER-beta2 to total ER-beta. Quercetin did not alter the total levels nor the percent distribution of ER-beta isoforms in either cell line. Genistein, through the modulation of ER-beta isoform RNA expression inhibited estrogen-promoted cell growth, without interfering on estrogen-regulated transcription. ER-beta and its ER-beta mRNA isoforms may be involved in a self-limiting mechanism of estrogenic stimulation promoted either by the natural hormone or by weaker estrogen agonists like genistein.
富含植物雌激素的食物的高摄入量与乳腺癌发病率的降低相关。然而，在将植物雌激素用作化学预防策略时，植物雌激素对已存在的乳腺肿瘤生长的影响令人担忧。染料木黄酮是大豆中的活性植物雌激素，通过雌激素受体（ER）介导表现出弱雌激素活性，对ER-β亚型具有优先结合。然而，目前尚无关于植物雌激素与可变剪接产生的各种异构体之间相互作用的信息。在两种表达不同水平ER-β的人乳腺癌细胞系T47D和BT20中，单独评估染料木黄酮和槲皮素的作用，并与17β-雌二醇进行比较，通过三重引物RT-PCR测定法评估雌激素受体-β（ER-β）异构体的mRNA表达。在T47D细胞中，雌二醇使总ER-β上调6倍，并改变了各种异构体的相对表达模式，上调β2并下调β5异构体。染料木黄酮在T47D细胞中上调ER-β2和ER-β1，处理后ER-β2异构体变得普遍，而在BT20细胞中，它使ER-β1和ER-β2对总ER-β的贡献百分比几乎增加了一倍。槲皮素在两种细胞系中均未改变ER-β异构体的总水平或百分比分布。染料木黄酮通过调节ER-β异构体RNA表达抑制雌激素促进的细胞生长，而不干扰雌激素调节的转录。ER-β及其ER-βmRNA异构体可能参与由天然激素或像染料木黄酮这样较弱的雌激素激动剂促进的雌激素刺激的自我限制机制。
