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Loss
of PTEN facilitates HIF-1-mediated gene expression
Zundel W, Schindler C, Haas-Kogan D, Koong A, Kaper F, Chen E, Gottschalk AR,
Ryan HE, Johnson RS, Jefferson AB, Stokoe D, Giaccia AJ
Mayer Cancer Biology Research Laboratory, Department of Radiation
Oncology, Stanford University, Stanford, California 94305-5468 USA
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.
PMID: 10691731 [PubMed - indexed for MEDLINE]
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