Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Mol Med Rep. 2011 Mar-Apr;4(2):215-9. doi: 10.3892/mmr.2011.412. Epub 2011 Jan 3.
Estrogen receptor α (ERα) mediates most of the biological effects of estrogen in mammary epithelial cells and stimulates growth signals involving phosphoinositide-3-OH kinase (PI3K)/Akt in breast cancer cells. Phosphatase and tensin homologue (PTEN) is a critical counter-regulator of PI3K signaling and is thus one of the major tumor suppressors in breast cancer. Inhibition of PI3K with an inhibitor, wortmannin, increased the level of PTEN protein in ERα-positive MCF-7 cells, while levels in ERα-negative MDA-MB 231 cells were not altered. In addition, the level of PTEN protein in MCF-7 cells was significantly lower than that in MDA-MB 231 cells, which correlated with high levels of phospho-Akt and phosphatidylinositol-3,4,5,-trisphosphate (PIP3). However, PTEN mRNA expression as measured by real-time PCR showed no differences in either cell line. Notably, the levels of casein kinase 2 (CK2) and phospho-PTEN (Ser380/Thr382/383) in MCF-7 cells were lower than those in MDA-MB 231 cells, indicating that the down-regulation of PTEN protein in MCF-7 cells is caused by low levels of CK2 expression, leading to accelerated PTEN degradation. Collectively, these results suggest that ERα induces the down-regulation of PTEN through PI3K activation in breast cancer cells.
雌激素受体 α (ERα) 介导了雌激素在乳腺上皮细胞中的大部分生物学效应，并刺激涉及乳腺癌细胞中磷酸肌醇-3-激酶 (PI3K)/Akt 的生长信号。磷酸酶和张力蛋白同源物 (PTEN) 是 PI3K 信号的关键负调节剂，因此是乳腺癌中的主要肿瘤抑制因子之一。用抑制剂渥曼青霉素抑制 PI3K，增加了 ERα 阳性 MCF-7 细胞中 PTEN 蛋白的水平，而 ERα 阴性 MDA-MB 231 细胞中的水平没有改变。此外，MCF-7 细胞中 PTEN 蛋白的水平明显低于 MDA-MB 231 细胞，这与磷酸化 Akt 和磷脂酰肌醇-3,4,5-三磷酸 (PIP3) 的高水平相关。然而，实时 PCR 测量的 PTEN mRNA 表达在两种细胞系中均无差异。值得注意的是，MCF-7 细胞中的酪蛋白激酶 2 (CK2) 和磷酸化-PTEN (Ser380/Thr382/383) 水平低于 MDA-MB 231 细胞，表明 MCF-7 细胞中 PTEN 蛋白的下调是由于 CK2 表达水平低，导致 PTEN 降解加速。综上所述，这些结果表明 ERα 通过 PI3K 激活诱导乳腺癌细胞中 PTEN 的下调。
