雌激素受体β抑制17β-雌二醇刺激的乳腺癌细胞系T47D的增殖。
Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D.
作者信息
Ström Anders, Hartman Johan, Foster James S, Kietz Silke, Wimalasena Jay, Gustafsson Jan-Ake
机构信息
Department of Biosciences, Karolinska Institutet, Novum, S-14157 Huddinge, Sweden.
出版信息
Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1566-71. doi: 10.1073/pnas.0308319100. Epub 2004 Jan 26.
Abstract
Estrogen receptor (ER) beta counteracts the activity of ERalpha in many systems. In agreement with this, we show in this study that induced expression of ERbeta in the breast cancer cell line T47D reduces 17beta-estradiol-stimulated proliferation when expression of ERbeta mRNA equals that of ERalpha. Induction of ERbeta reduces growth of exponentially proliferating cells with a concomitant decrease in components of the cell cycle associated with proliferation, namely cyclin E, Cdc25A (a key regulator of Cdk2), p45(Skp2) (a key regulator of p27(Kip1) proteolysis), and an increase in the Cdk inhibitor p27(Kip1). We also observed a reduced Cdk2 activity. These findings suggest a possible role for ERbeta in breast cancer and imply that ERbeta-specific ligands may reduce proliferation of ER-positive breast cancer cells through actions on the G(1) phase cell-cycle machinery.
摘要
雌激素受体（ER）β在许多系统中可对抗ERα的活性。与此一致的是，我们在本研究中发现，当乳腺癌细胞系T47D中ERβ的mRNA表达量与ERα相等时，ERβ的诱导表达会降低17β-雌二醇刺激的细胞增殖。ERβ的诱导会减少指数增殖细胞的生长，同时与增殖相关的细胞周期成分减少，即细胞周期蛋白E、Cdc25A（Cdk2的关键调节因子）、p45（Skp2）（p27（Kip1）蛋白水解的关键调节因子），并使细胞周期蛋白依赖性激酶抑制剂p27（Kip1）增加。我们还观察到Cdk2活性降低。这些发现提示ERβ在乳腺癌中可能发挥作用，并暗示ERβ特异性配体可能通过作用于G1期细胞周期机制来减少ER阳性乳腺癌细胞的增殖。
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