Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo.

Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Research Abstract Details 

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Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Abstract Text:

Deregulated signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is common in many types of cancer, including glioblastoma. Dissecting the molecular events associated with activation of this pathway in glioblastoma patients in vivo presents an important challenge that has implications for the development and clinical testing of PI3K pathway inhibitors. Using an immunohistochemical analysis applied to a tissue microarray, we performed hierarchical clustering and multidimensional scaling, as well as univariate and multivariate analyses, to dissect the PI3K pathway in vivo. We demonstrate that loss of the tumor suppressor protein PTEN, which antagonizes PI3K pathway activation, is highly correlated with activation of the main PI3K effector Akt in vivo. We also show that Akt activation is significantly correlated with phosphorylation of mammalian target of rapamycin (mTOR), the family of forkhead transcription factors (FOXO1, FOXO3a, and FOXO4), and S6, which are thought to promote its effects. Expression of the mutant epidermal growth factor receptor vIII is also tightly correlated with phosphorylation of these effectors, demonstrating an additional route to PI3K pathway activation in glioblastomas in vivo. These results provide the first dissection of the PI3K pathway in glioblastoma in vivo and suggest an approach to stratifying patients for targeted kinase inhibitor therapy.

Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Publishing Authors By Initials

For similar proteins: neoplasm proteins: tumor suppressor proteins research abstracts see: proteins: neoplasm proteins: tumor suppressor proteins research

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Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 63

Page Numbers: 2742-6

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Jun

YEAR: 2003

Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Proteins

MESH TERMS: biosynthesis

Chemical & Substance for Abstract: Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo. Information

Substance Name: PTEN Phosphohydrolase

Registry Number: EC 3.1.3.67

Grant and Affiliation Information for Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo.

AFFILIATION: Departments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.

Country: United States

AGENCY: United States NCI

GRANT: U01 CA88127

ACRONYM: CA

MEDLINETA: Cancer Res

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