1. Loss of PTEN facilitates HIF-1-mediated gene expression
- Author
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Heather E. Ryan, Daphne A. Haas-Kogan, Wayne Zundel, Cornelia Schindler, Anne B. Jefferson, Fiona Kaper, Eunice Y. Chen, Alexander Gottschalk, David Stokoe, Amato J. Giaccia, Randall S. Johnson, and Albert C. Koong
- Subjects
Regulation of gene expression ,Vascular endothelial growth factor A ,biology ,DNA synthesis ,Gene expression ,Genetics ,biology.protein ,Cancer research ,PTEN ,Transfection ,Protein kinase B ,Transcription factor ,Developmental Biology - Abstract
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-1α stabilization, whereas PTEN attenuates hypoxia-mediated HIF-1α stabilization. We propose that loss ofPTEN during malignant progression contributes to tumor expansion through the deregulation of Akt activity and HIF-1-regulated gene expression.
- Published
- 2000