Zundel W, Schindler C, Haas-Kogan D, Koong A, Kaper F, Chen E, Gottschalk A R, Ryan H E, Johnson R S, Jefferson A B, Stokoe D, Giaccia A J
Mayer Cancer Biology Research Laboratory, Department of Radiation Oncology, Stanford University, Stanford, California 94305-5468 USA.
Genes Dev. 2000 Feb 15;14(4):391-6.
In glioblastoma-derived cell lines, PTEN does not significantly alter apoptotic sensitivity or cause complete inhibition of DNA synthesis. However, in these cell lines PTEN regulates hypoxia- and IGF-1-induced angiogenic gene expression by regulating Akt activation of HIF-1 activity. Restoration of wild-type PTEN to glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes. In addition, Akt activation leads to HIF-1alpha stabilization, whereas PTEN attenuates hypoxia-mediated HIF-1alpha stabilization. We propose that loss of PTEN during malignant progression contributes to tumor expansion through the deregulation of Akt activity and HIF-1-regulated gene expression.
在胶质母细胞瘤衍生的细胞系中，PTEN 不会显著改变凋亡敏感性，也不会完全抑制 DNA 合成。然而，在这些细胞系中，PTEN 通过调节 Akt 对 HIF-1 活性的激活来调控缺氧和 IGF-1 诱导的血管生成基因表达。将野生型 PTEN 恢复到缺乏功能性 PTEN 的胶质母细胞瘤细胞系中，可消除缺氧和 IGF-1 对 HIF-1 调控基因的诱导作用。此外，Akt 激活导致 HIF-1α 稳定，而 PTEN 减弱缺氧介导的 HIF-1α 稳定。我们提出，恶性进展过程中 PTEN 的缺失通过 Akt 活性失调和 HIF-1 调控基因表达促进肿瘤扩张。
