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Loss of PTEN facilitates HIF-1-mediated gene expression.

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-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.

SUBMITTER: Zundel W

PROVIDER: S-EPMC316386 | biostudies-literature | 2000 Feb

REPOSITORIES: biostudies-literature

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Loss of PTEN facilitates HIF-1-mediated gene expression.

Zundel W W Schindler C C Haas-Kogan D D Koong A A Kaper F F Chen E E Gottschalk A R AR Ryan H E HE Johnson R S RS Jefferson A B AB Stokoe D D Giaccia A J AJ

Genes & development 20000201 4

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 P ...[more]

PMID: 10691731

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