Up-regulation of PI3K/Akt signaling by 17β-estradiol through activation of estrogen receptor-α but not estrogen receptor-β, and stimulates cell growth in breast cancer cells
Up-regulation of PI3K/Akt signaling by 17β-estradiol through activation of estrogen receptor-α but not estrogen receptor-β, and stimulates cell growth in breast cancer cells
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DOI：
10.1016/j.bbrc.2005.08.256
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发表时间：
2005-11-04
影响因子：
3.1
通讯作者：
Jung, SH
中科院分区：
文献类型：
--
作者：
Lee, YR;Park, J;Jung, SH
雌激素刺激乳腺癌细胞增殖。雌激素的生物学效应通过两种细胞内受体介导，雌激素受体-α（ER α）和雌激素受体-β（ER β）。然而，ER在雌激素增殖作用中的作用尚未完全确定。最近，已经知道ER通过与磷脂酰肌醇-3-OH激酶（PI3K）的p85调节亚基结合来激活PI3K。因此，可能的机制可能包括ER介导的磷酸肌醇代谢，随后形成磷脂酰肌醇-3，4，5-。三磷酸肌醇（PIP3），其通过PI3K活化由磷脂酰肌醇4，5-二磷酸产生。本研究表明，17 β-雌二醇（E2）以ER α依赖性方式上调PI 3 K，但不上调ER β，并刺激乳腺癌细胞的细胞生长。为了研究这种现象，我们用10 nM E2处理ER α阳性MCF-7细胞和ER α阴性MDA-MB-231细胞。用E2处理MCF-7细胞导致PI3K（p85）表达的显著增加，这导致磷酸化Akt（Ser-473）和PIP3水平的增加。这些观察结果也与E2诱导的细胞增殖活性增加相关。然而，在MDA-MB-231细胞系中未观察到E2对乳腺癌细胞的这些作用，表明E2介导的PI3K/Akt通路的上调是ER α依赖性的。这些结果表明，雌激素通过ER α依赖性机制激活MCF-7细胞中的PI3K/Akt信号。(c)2005年爱思唯尔公司All rights reserved.
Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5.-trisphosphate (PIP3) which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17 beta-estradiol (E2) up-regulates PI3K in an ER alpha-dependent manner, but not ER beta, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ER alpha-positive MCF-7 cells and ER alpha-negative MDA-MB-231 cells with 10 nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP3 level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ER alpha-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ER alpha-dependent mechanism in MCF-7 cells. (c) 2005 Elsevier Inc. All rights reserved.