Loss of PTEN facilitates HIF-1-mediated gene expression.
By W. Zundel, C. Schindler, D. Haas-Kogan, A. Koong, F. Kaper, E. Chen, A. Gottschalk, H. E. Ryan, Richard J. Johnson, A. B. Jefferson and 2 more. Genes & Development, 2000
923 citations recorded by the source corpus.
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.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/543b9e135eb95ffc87666fd99e3772ddad33dca3
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
- G. Semenza
- C. V. Dang
- Richard J. Johnson
- Amato J. Giaccia
- Roland H. Wenger
- D. Liao
- Adrian L. Harris
- W. Koppenol
In Molecular Biology
- G. Semenza
- C. V. Dang
- Amato J. Giaccia
- Richard J. Johnson
- R. Abraham
- W. Koppenol
- P. L. Bounds
- D. Liao
Citations in the corpus
- Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression (2001, background): “Because dysregulation or enhanced activation of HIF-1α function has been implicated in a variety of pathological conditions including induced tumour growth rate”
- Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. (2005, background): “Overexpression of recombinant PTEN in glioma cells leads to marked reduction in HIF-1 expression (Zundel et al., 2000).”
- Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin (2002, background): “Although oxygen tension plays a determinant role in the process of HIF-1 activation, the amplitude of this response is modulated by growth factor-dependent signaling pathways, including the Ras-Erk and phosphoinositide 3-kinase (PI 3-kinase)/AKT cascades (23, 50, 52).”
- Cellular adaptation to hypoxia: O2‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O2‐regulated gene expression (2002, background): “Specific inhibition of the PI3-kinase was shown to inhibit many of the HIF-1-dependent cellular responses (103–106) and loss of the tumor suppressor function of PTEN facilitated HIF-1-mediated gene expression (107).”
- Otto Warburg's contributions to current concepts of cancer metabolism (2011, background): “Other tumour suppressor genes and proteins have also been implicated as modulators of HIF1α, and thereby might contribute to the Warburg effect; for example, HIF1-mediated gene expression is facilitated by loss of the PTEN tumour suppressor gen”