Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC

Daphne Haas-Kogan, Noga Shalev, Michelle Wong, Gordon Mills, Garret Yount, David Stokoe

Research output: Contribution to journalArticle

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Abstract

Glioblastomas are highly malignant tumors of the central nervous system that are resistant to radiation and chemotherapy [1]. We explored the role of the phosphatidylinositol (PI) 3-kinase signal transduction pathway in glioblastomas, as this pathway has been shown to inhibit apoptosis induced by cytokine withdrawal and the detachment of cells from the extracellular matrix [2]. Components of this pathway have been implicated in tumor development [3-6]. We show that glioblastoma cells, in contrast to primary human astrocytes, contain high endogenous protein kinase B (PKB/Akt) activity and high levels of PI 3,4,5-triphosphate (PI(3,4,5)P3) and PI(3,4)P2, the lipid products of PI 3-kinase. These glioblastoma cells express mutant forms of the putative 3' phospholipid phosphatase PTEN, also known as MMAC. Expression of wild-type PTEN derived from primary astrocytes, but not of mutant forms of PTEN, reduced the levels of 3' phosphoinositides and inhibited PKB/Akt activity. PTEN antagonized the activation of PKB/Akt by growth factors, by activated PI 3-kinase and by PI-dependent protein kinase-1 (PDK1), but did not antagonize the phospholipid-independent activation of PKB/Akt lacking the pleckstrin homology (PH) domain. These results suggest a role for PTEN in regulating the activity of the PI 3-kinase pathway in malignant human cells.

Original languageEnglish (US)
Pages (from-to)1195-1198
Number of pages4
JournalCurrent Biology
Volume8
Issue number21
StatePublished - Oct 22 1998
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Genetic Suppression
Proto-Oncogene Proteins c-akt
phosphatidylinositols
phosphatidylinositol 3-kinase
Glioblastoma
Phosphatidylinositols
protein kinases
Tumors
mutation
neoplasms
astrocytes
Astrocytes
Neoplasms
Phospholipids
phospholipids
Chemical activation
pleckstrin
PTEN Phosphohydrolase
cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. / Haas-Kogan, Daphne; Shalev, Noga; Wong, Michelle; Mills, Gordon; Yount, Garret; Stokoe, David.

In: Current Biology, Vol. 8, No. 21, 22.10.1998, p. 1195-1198.

Research output: Contribution to journalArticle

Haas-Kogan, D, Shalev, N, Wong, M, Mills, G, Yount, G & Stokoe, D 1998, 'Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC', Current Biology, vol. 8, no. 21, pp. 1195-1198.
Haas-Kogan, Daphne ; Shalev, Noga ; Wong, Michelle ; Mills, Gordon ; Yount, Garret ; Stokoe, David. / Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. In: Current Biology. 1998 ; Vol. 8, No. 21. pp. 1195-1198.
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