PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells

In response to genotoxic stress, p53 induces the tumor suppressors maspin and PTEN.  Here we demonstrate that in response to limited oxygen conditions PTEN and p53 work in tandem to induce maspin in glioblastoma cells. In response to hypoxia a portion of PTEN migrates to the nucleus and complexes wi...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2009-03, Vol.8 (6), p.896-901
Main Authors: Eitel, Jacob A., Bijangi-Vishehsaraei, Khadijeh, Saadatzadeh, M. Reza, Murphy, Michael P., Pollok, Karen E., Mayo, Lindsey D.
Format: Article
Language:English
Subjects:
Animals
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Hypoxia
Cell Line, Tumor
Cycle
Glioblastoma - metabolism
Glioblastoma - pathology
Humans
Landes
Mice
Mice, Nude
Organogenesis
Proteins
PTEN Phosphohydrolase - metabolism
Serpins - biosynthesis
Transplantation, Heterologous
Tumor Suppressor Protein p53 - metabolism
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Summary:In response to genotoxic stress, p53 induces the tumor suppressors maspin and PTEN.  Here we demonstrate that in response to limited oxygen conditions PTEN and p53 work in tandem to induce maspin in glioblastoma cells. In response to hypoxia a portion of PTEN migrates to the nucleus and complexes with p53, while cytoplasmic PTEN prevents Mdm2 nuclear localization by attenuating Akt signaling. Subcellular distribution of PTEN in the cytoplasm or nucleus protects p53 from inac-tivation and degradation. The presence of nuclear PTEN and p53 coordinates the induction of maspin and p21 (both p53 gene targets) in response to hypoxia. Altering the expression of PTEN and/or p53 attenuated maspin gene induction under hypoxic conditions. Furthermore, implanting U87 (PTEN null) and PTEN reconstituted U87 cells (U87PTEN) in mice we observed by immuno-histochemistry and western blot that Maspin was only detectable in cells with PTEN.  The integra-tion of PTEN and p53 into a common pathway for the induction of another tumor suppressor, Maspin, constitutes a tumor suppressor network of PTEN/p53/Mapsin that is operational under limited oxygen conditions.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.8.6.7899