Evidence for phosphatidylinositol 3-kinase-Akt-p70S6K pathway activation and transduction of mitogenic signals by platelet-derived growth factor in meningioma cells

Mahlon Johnson, Evelyn Okediji, Ann Woodard, Steven A. Toms, George S. Allen

Research output: Contribution to journalArticle

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Abstract

Object. The intracellular events transducing mitogenic signals from platelet-derived growth factor-β (PDGFβ) receptor tyrosine kinases are not precisely known. In this study the authors evaluated whether the phosphatidylinositol 3-kinase (PI3-K)-Akt-p70S6K pathway is expressed in meningiomas, regulates their growth, and transduces mitogenic signals of PDGF-BB. Methods. Nine meningioma tumors obtained in humans were evaluated using Western blot analysis for phosphorylated (activated) Akt and phosphorylated p70S6K. Cells cultured from seven of these meningiomas were also screened using Western blot analysis for Akt and for phosphorylated Akt and p70S6K. The authors also evaluated whether PDGF-BB stimulation of meningioma cells was associated with the phosphorylation of Akt and p70S6K known to activate these kinases. In addition, the effects of wortmannin, an inhibitor of PI3-K, on proliferation and activation of Akt and p70S6K in meningioma cells stimulated with PDGF-BB were evaluated. Western blots of lysates from meningiomas demonstrated phosphorylated Akt and p70S6K. Treatment with PDGF-BB stimulated phosphorylation of Akt and p70S6K in each meningioma cell culture. Wortmannin (500 and 1000 nM) significantly decreased PDGF-BB stimulation of meningioma cells (p < 0.001) while it reduced Akt and p70S6K phosphorylation but not mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation. Conclusions. These findings indicate that Akt and p70S6K are constitutively expressed and activated in meningioma cells and that the PI3-K-Akt-p70S6K pathway may participate in transduction of mitogenic signals in meningiomas independent of the Raf-1-MEK-1-MAPK/ERK cascade.

Original languageEnglish (US)
Pages (from-to)668-675
Number of pages8
JournalJournal of Neurosurgery
Volume97
Issue number3
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Phosphatidylinositol 3-Kinase
70-kDa Ribosomal Protein S6 Kinases
Platelet-Derived Growth Factor
Meningioma
Signal Transduction
Phosphorylation
Western Blotting
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase Kinases
Cultured Cells
Phosphotransferases
Cell Culture Techniques
platelet-derived growth factor BB

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Evidence for phosphatidylinositol 3-kinase-Akt-p70S6K pathway activation and transduction of mitogenic signals by platelet-derived growth factor in meningioma cells. / Johnson, Mahlon; Okediji, Evelyn; Woodard, Ann; Toms, Steven A.; Allen, George S.

In: Journal of Neurosurgery, Vol. 97, No. 3, 01.01.2002, p. 668-675.

Research output: Contribution to journalArticle

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title = "Evidence for phosphatidylinositol 3-kinase-Akt-p70S6K pathway activation and transduction of mitogenic signals by platelet-derived growth factor in meningioma cells",
abstract = "Object. The intracellular events transducing mitogenic signals from platelet-derived growth factor-β (PDGFβ) receptor tyrosine kinases are not precisely known. In this study the authors evaluated whether the phosphatidylinositol 3-kinase (PI3-K)-Akt-p70S6K pathway is expressed in meningiomas, regulates their growth, and transduces mitogenic signals of PDGF-BB. Methods. Nine meningioma tumors obtained in humans were evaluated using Western blot analysis for phosphorylated (activated) Akt and phosphorylated p70S6K. Cells cultured from seven of these meningiomas were also screened using Western blot analysis for Akt and for phosphorylated Akt and p70S6K. The authors also evaluated whether PDGF-BB stimulation of meningioma cells was associated with the phosphorylation of Akt and p70S6K known to activate these kinases. In addition, the effects of wortmannin, an inhibitor of PI3-K, on proliferation and activation of Akt and p70S6K in meningioma cells stimulated with PDGF-BB were evaluated. Western blots of lysates from meningiomas demonstrated phosphorylated Akt and p70S6K. Treatment with PDGF-BB stimulated phosphorylation of Akt and p70S6K in each meningioma cell culture. Wortmannin (500 and 1000 nM) significantly decreased PDGF-BB stimulation of meningioma cells (p < 0.001) while it reduced Akt and p70S6K phosphorylation but not mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation. Conclusions. These findings indicate that Akt and p70S6K are constitutively expressed and activated in meningioma cells and that the PI3-K-Akt-p70S6K pathway may participate in transduction of mitogenic signals in meningiomas independent of the Raf-1-MEK-1-MAPK/ERK cascade.",
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T1 - Evidence for phosphatidylinositol 3-kinase-Akt-p70S6K pathway activation and transduction of mitogenic signals by platelet-derived growth factor in meningioma cells

AU - Johnson, Mahlon

AU - Okediji, Evelyn

AU - Woodard, Ann

AU - Toms, Steven A.

AU - Allen, George S.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Object. The intracellular events transducing mitogenic signals from platelet-derived growth factor-β (PDGFβ) receptor tyrosine kinases are not precisely known. In this study the authors evaluated whether the phosphatidylinositol 3-kinase (PI3-K)-Akt-p70S6K pathway is expressed in meningiomas, regulates their growth, and transduces mitogenic signals of PDGF-BB. Methods. Nine meningioma tumors obtained in humans were evaluated using Western blot analysis for phosphorylated (activated) Akt and phosphorylated p70S6K. Cells cultured from seven of these meningiomas were also screened using Western blot analysis for Akt and for phosphorylated Akt and p70S6K. The authors also evaluated whether PDGF-BB stimulation of meningioma cells was associated with the phosphorylation of Akt and p70S6K known to activate these kinases. In addition, the effects of wortmannin, an inhibitor of PI3-K, on proliferation and activation of Akt and p70S6K in meningioma cells stimulated with PDGF-BB were evaluated. Western blots of lysates from meningiomas demonstrated phosphorylated Akt and p70S6K. Treatment with PDGF-BB stimulated phosphorylation of Akt and p70S6K in each meningioma cell culture. Wortmannin (500 and 1000 nM) significantly decreased PDGF-BB stimulation of meningioma cells (p < 0.001) while it reduced Akt and p70S6K phosphorylation but not mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation. Conclusions. These findings indicate that Akt and p70S6K are constitutively expressed and activated in meningioma cells and that the PI3-K-Akt-p70S6K pathway may participate in transduction of mitogenic signals in meningiomas independent of the Raf-1-MEK-1-MAPK/ERK cascade.

AB - Object. The intracellular events transducing mitogenic signals from platelet-derived growth factor-β (PDGFβ) receptor tyrosine kinases are not precisely known. In this study the authors evaluated whether the phosphatidylinositol 3-kinase (PI3-K)-Akt-p70S6K pathway is expressed in meningiomas, regulates their growth, and transduces mitogenic signals of PDGF-BB. Methods. Nine meningioma tumors obtained in humans were evaluated using Western blot analysis for phosphorylated (activated) Akt and phosphorylated p70S6K. Cells cultured from seven of these meningiomas were also screened using Western blot analysis for Akt and for phosphorylated Akt and p70S6K. The authors also evaluated whether PDGF-BB stimulation of meningioma cells was associated with the phosphorylation of Akt and p70S6K known to activate these kinases. In addition, the effects of wortmannin, an inhibitor of PI3-K, on proliferation and activation of Akt and p70S6K in meningioma cells stimulated with PDGF-BB were evaluated. Western blots of lysates from meningiomas demonstrated phosphorylated Akt and p70S6K. Treatment with PDGF-BB stimulated phosphorylation of Akt and p70S6K in each meningioma cell culture. Wortmannin (500 and 1000 nM) significantly decreased PDGF-BB stimulation of meningioma cells (p < 0.001) while it reduced Akt and p70S6K phosphorylation but not mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation. Conclusions. These findings indicate that Akt and p70S6K are constitutively expressed and activated in meningioma cells and that the PI3-K-Akt-p70S6K pathway may participate in transduction of mitogenic signals in meningiomas independent of the Raf-1-MEK-1-MAPK/ERK cascade.

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