PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway.

PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Research Abstract Details 

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PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Abstract Text:

Dimpy Koul,Ruijun Shen,Shishir Shishodia,Yasanuri Takada,Krishna P Bhat,Shrikanth A G Reddy,Bharat B Aggarwal,W K Alfred Yung,

The continual activation of signaling cascades results in dramatic consequences that include loss of cellular growth control and neoplastic transformation. We show here that phosphoinositide 3-kinase and its mediator Akt was constitutively activated in glioma and that this might be due to the aberrant expression of their natural antagonist PTEN. The PTEN (phosphatase and tensin homologue deleted on chromosome ten) tumor suppressor gene modulates cell growth and survival through mechanisms that are incompletely understood. In this study, we investigated the possibility that PTEN mediates its effects through modulation of transcription factor AP-1, which is in part due to decrease in c-fos expression which was dependent on PI3kinase activity. Consistent with a reduction in the c-fos levels, an AP-1 dependent reporter gene was poorly induced in the PTEN expressing cell lines. In contrast to its effect on c-fos, PTEN did not affect the expression of c-Jun and other fos family members. We also show that the effect of PTEN on c-fos expression was due to its ability to antagonize PI3-kinase and could be mimicked by the expression of dominant negative Akt mutant. Taken together, these data indicate that the aberrant expression of PTEN contributes to the activation of the PI3kinase/Akt pathway and its transcription factor mediators in glioma. We conclude that the ectopic expression of PTEN down regulates the proliferation of glioma cells through the suppression of AP-1 and that this target might be essential for its central role in the growth and survival of glioma cancer cells.

PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Publishing Authors By Initials

D Koul,R Shen,S Shishodia,Y Takada,KP Bhat,SA Reddy,BB Aggarwal,WK Yung,

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

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PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biochemistry

VOLUME: 300

Page Numbers: 77-87

Journal Abbreviation: Mol. Cell. Biochem.

ISSN: 0300-8177

DAY: 18

MONTH: 01

YEAR: 2007

PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 364456

PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: pharmacology

Chemical & Substance for Abstract: PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway. Information

Substance Name: PTEN Phosphohydrolase

Registry Number: EC 3.1.3.67

Grant and Affiliation Information for PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3-kinase/Akt pathway.

AFFILIATION: Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. Dkoul@mdanderson.org

Country: Netherlands

AGENCY: United States NCI

GRANT: R01 CA 056041

ACRONYM: CA

MEDLINETA: Mol Cell Biochem

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