Hlobilkova Alice, Knillova Jana, Svachova Michaela, Skypalova Petra, Krystof Vladimir, Kolar Zdenek
Institute of Pathology and Laboratory of Molecular Pathology, Faculty of Medicine, Palacky University, Hnevotinska 3, Olomouc CZ-775 15, Czech Republic.
Anticancer Res. 2006 Mar-Apr;26(2A):1015-22.
PTEN is a tumour suppressor protein with phosphatase activity frequently altered in several types of human cancers.
The PTEN effect was studied on the cell cycle (by bromdeoxyuridine incorporation) and on the phosphatidylinositol-3-kinase/protein kinase B/Akt (PI3-K/PKB/Akt) pathway regulating proteins (by immunocytochemical, Western blot analysis and kinase assay) upon transfection of wild-type PTEN and its mutant H123Y in breast cancer cell lines.
The expression of the important proteins in the MCF-7 and BT-549 cells was characterised and the cellular localisation of PTEN was analysed. Transfection of H123Y led to the down-regulation of p27(Kip1) and p21(Waf1/Cip1) protein levels and the up-regulation of phosphorylated PKB/Akt. An overexpression of PTEN decreased cyclin E/cdk2 activity and inhibited S-phase entry in MCF-7. In BT-549 these changes were not observed, but overexpression of PTEN led to a diminution of PKB/Akt phosphorylation.
PTEN function is mediated through the inhibition of the cell cycle and PKB/Akt phosphorylation in breast cancer cells.
PTEN是一种具有磷酸酶活性的肿瘤抑制蛋白，在多种人类癌症中经常发生改变。
在乳腺癌细胞系中转染野生型PTEN及其突变体H123Y后，通过溴脱氧尿苷掺入研究PTEN对细胞周期的影响，并通过免疫细胞化学、蛋白质印迹分析和激酶测定研究其对磷脂酰肌醇-3-激酶/蛋白激酶B/Akt（PI3-K/PKB/Akt）信号通路调节蛋白的影响。
对MCF-7和BT-549细胞中重要蛋白的表达进行了表征，并分析了PTEN的细胞定位。H123Y转染导致p27（Kip1）和p21（Waf1/Cip1）蛋白水平下调以及磷酸化PKB/Akt上调。PTEN的过表达降低了细胞周期蛋白E/cdk2活性并抑制了MCF-7细胞进入S期。在BT-549细胞中未观察到这些变化，但PTEN的过表达导致PKB/Akt磷酸化减少。
PTEN的功能是通过抑制乳腺癌细胞的细胞周期和PKB/Akt磷酸化来介导的。
