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Biphasic estradiol-induced AKT phosphorylation is modulated by PTEN via MAP kinase in HepG2 cells

机译:PTEN通过MAP激酶在HepG2细胞中调节双相雌二醇诱导的AKT磷酸化

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We reported previously in HepG2 cells that estradiol induces cell cycle progression throughout the G(1)-S transition by the parallel stimulation of both PKC-alpha and ERK signaling molecules. The analysis of the cyclin D, gene expression showed that only the MAP kinase pathway was involved. Here, the presence of rapidongenomic, estradiol-regulated, P13K/AKT signal transduction pathway, its modulation by the levels of the tumor suppressor PTEN, its cross-talk with the ERK pathway, and its involvement in DNA synthesis and cyclin D-1 gene promoter activity have all been studied in HepG2 cells. 17beta-Estradiol induced the rapid and biphasic phosphorylation of AKT. These phosphorylations were independent of each other, being the first wave of activation independent of the estrogen receptor (ER), whereas the second was dependent on ER. Both activations were dependent on PI3K activity; furthermore, the ERK pathway modulated AKT phosphorylation by acting on the PTEN levels. The results showed that the PI3K pathway, as well as ER, were strongly involved in both G(1)-S progression and cyclin D-1 promoter activity by acting on its proximal region (-254 base pairs). These data indicate that in HepG2 cells, different rapidongenomic estradiol-induced signal transduction pathways modulate the multiple steps of G(1)-S phase transition. [References: 53]
机译:我们以前在HepG2细胞中报道过,雌二醇通过平行刺激PKC-α和ERK信号分子来诱导整个G(1)-S过渡的细胞周期进程。对细胞周期蛋白D,基因表达的分析表明仅涉及MAP激酶途径。在这里,存在快速/非基因组,雌二醇调节的P13K / AKT信号转导途径,其受肿瘤抑制物PTEN水平的调节,与ERK途径的相互作用以及其参与DNA合成和细胞周期蛋白D-已经在HepG2细胞中研究了1个基因启动子的活性。 17β-雌二醇诱导AKT的快速和双相磷酸化。这些磷酸化彼此独立,是第一波激活波,独立于雌激素受体(ER),而第二波依赖于ER。两种激活均依赖于PI3K活性。此外,ERK途径通过作用于PTEN水平来调节AKT磷酸化。结果表明,PI3K途径以及ER,通过作用于其近端区域(-254个碱基对),强烈参与了G(1)-S的进展和细胞周期蛋白D-1启动子的活性。这些数据表明,在HepG2细胞中,不同的快速/非基因组雌二醇诱导的信号转导途径可调节G(​​1)-S相变的多个步骤。 [参考:53]

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