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

Jacob A. Eitel, Khadijeh Bijangi-Vishehsaraei, M. Reza Saadatzadeh, Janak R. Bhavsar, Michael Murphy, Karen Pollok, Lindsey Mayo

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 inactivation 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 immunohistochemistry and western blot that Maspin was only detectable in cells with PTEN. The integration 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.

Original languageEnglish
Pages (from-to)896-901
Number of pages6
JournalCell Cycle
Volume8
Issue number6
StatePublished - Mar 15 2009

Fingerprint

Glioblastoma
Oxygen
Neoplasms
p53 Genes
DNA Damage
SERPIN-B5
Hypoxia
Cytoplasm
Western Blotting
Immunohistochemistry
Genes

Keywords

  • Glioblastoma
  • HDM2
  • Hypoxia
  • Maspin
  • MDM2
  • P53
  • PTEN

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Eitel, J. A., Bijangi-Vishehsaraei, K., Saadatzadeh, M. R., Bhavsar, J. R., Murphy, M., Pollok, K., & Mayo, L. (2009). PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells. Cell Cycle, 8(6), 896-901.

PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells. / Eitel, Jacob A.; Bijangi-Vishehsaraei, Khadijeh; Saadatzadeh, M. Reza; Bhavsar, Janak R.; Murphy, Michael; Pollok, Karen; Mayo, Lindsey.

In: Cell Cycle, Vol. 8, No. 6, 15.03.2009, p. 896-901.

Research output: Contribution to journalArticle

Eitel, JA, Bijangi-Vishehsaraei, K, Saadatzadeh, MR, Bhavsar, JR, Murphy, M, Pollok, K & Mayo, L 2009, 'PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells', Cell Cycle, vol. 8, no. 6, pp. 896-901.
Eitel JA, Bijangi-Vishehsaraei K, Saadatzadeh MR, Bhavsar JR, Murphy M, Pollok K et al. PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells. Cell Cycle. 2009 Mar 15;8(6):896-901.
Eitel, Jacob A. ; Bijangi-Vishehsaraei, Khadijeh ; Saadatzadeh, M. Reza ; Bhavsar, Janak R. ; Murphy, Michael ; Pollok, Karen ; Mayo, Lindsey. / PTEN and p53 are required for hypoxia induced expression of maspin in glioblastoma cells. In: Cell Cycle. 2009 ; Vol. 8, No. 6. pp. 896-901.
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