Insulin-Like Growth Factor Binding Protein 2 Promotes Glioma Development and Progression
Overexpression of insulin-like growth factor binding protein 2 (IGFBP2) is associated with progression in many types of human cancer. In this study we used a glial-specific transgenic mouse model to examine the active role of IGFBP2 in tumorigenesis and progression. Our studies show that IGFBP2 coexpression results in progression to a higher-grade glioma in platelet-derived growth factor β (PDGFB)-driven tumors. These anaplastic oligodendrogliomas are characterized by increased cellularity, vascular proliferation, small regions of necrosis, increased mitotic activity, and increased activation of the Akt pathway. Combined expression of IGFBP2 or Akt with K-Ras was required to form astrocytomas, indicating that activation of two separate pathways is necessary for gliomagenesis. In ex vivo experiments, blockade of Akt by an inhibitor led to decreased viability of cells coexpressing IGFBP2 versus PDGFB expression alone. Thus, this study provides definitive evidence that IGFBP2 plays a key role in activation of the Akt pathway and collaborates with K-Ras or PDGFB in the development and progression of two major types of glioma..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2007 |
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| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:104 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dunlap, Sarah M. [VerfasserIn] |
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| Links: |
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| Themen: |
Biological sciences |
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| PPN (Katalog-ID): |
JST069406987 |
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| 100 | 1 | |a Dunlap, Sarah M. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Insulin-Like Growth Factor Binding Protein 2 Promotes Glioma Development and Progression |
| 264 | 1 | |c 2007 | |
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| 520 | |a Overexpression of insulin-like growth factor binding protein 2 (IGFBP2) is associated with progression in many types of human cancer. In this study we used a glial-specific transgenic mouse model to examine the active role of IGFBP2 in tumorigenesis and progression. Our studies show that IGFBP2 coexpression results in progression to a higher-grade glioma in platelet-derived growth factor β (PDGFB)-driven tumors. These anaplastic oligodendrogliomas are characterized by increased cellularity, vascular proliferation, small regions of necrosis, increased mitotic activity, and increased activation of the Akt pathway. Combined expression of IGFBP2 or Akt with K-Ras was required to form astrocytomas, indicating that activation of two separate pathways is necessary for gliomagenesis. In ex vivo experiments, blockade of Akt by an inhibitor led to decreased viability of cells coexpressing IGFBP2 versus PDGFB expression alone. Thus, this study provides definitive evidence that IGFBP2 plays a key role in activation of the Akt pathway and collaborates with K-Ras or PDGFB in the development and progression of two major types of glioma. | ||
| 540 | |a Copyright 2007 The National Academy of Sciences of the United States of America | ||
| 650 | 4 | |a Glial-specific transgenic mouse model | |
| 650 | 4 | |a Oligodendroglioma | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Tumors | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Germ cell and embryonal neoplasms |x Glioma |x Oligodendroglioma | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Germ cell and embryonal neoplasms |x Glioma |x Astrocytoma | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Germ cell and embryonal neoplasms |x Glioma | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Cancer | |
| 650 | 4 | |a Biological sciences |x Biology |x Zoology |x Animals |x Mammals |x Rodents |x Mice | |
| 650 | 4 | |a Health sciences |x Medical sciences |x Immunology |x Immune system |x Immune response |x Adaptive immunity |x Active immunity |x Humoral immunity |x Antibodies | |
| 650 | 4 | |a Biological sciences |x Biology |x Genetics |x Molecular genetics |x Gene expression |x Gene expression regulation |x Up regulation | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Infections | |
| 650 | 4 | |a Biological sciences |x Biology |x Developmental biology |x Embryology |x Viability | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Tumors | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Germ cell and embryonal neoplasms |x Glioma |x Oligodendroglioma | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Germ cell and embryonal neoplasms |x Glioma |x Astrocytoma | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Germ cell and embryonal neoplasms |x Glioma | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Cancer | |
| 650 | 4 | |a Biological sciences |x Biology |x Zoology |x Animals |x Mammals |x Rodents |x Mice | |
| 650 | 4 | |a Health sciences |x Medical sciences |x Immunology |x Immune system |x Immune response |x Adaptive immunity |x Active immunity |x Humoral immunity |x Antibodies | |
| 650 | 4 | |a Biological sciences |x Biology |x Genetics |x Molecular genetics |x Gene expression |x Gene expression regulation |x Up regulation | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Infections | |
| 650 | 4 | |a Biological sciences |x Biology |x Developmental biology |x Embryology |x Viability | |
| 655 | 4 | |a research-article | |
| 700 | 1 | |a Celestino, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Rongcai |e verfasserin |4 aut | |
| 700 | 1 | |a Holland, Eric C. |e verfasserin |4 aut | |
| 700 | 1 | |a Fuller, Gregory N. |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 773 | 1 | 8 | |g volume:104 |g year:2007 |g number:28 |g pages:11736-11741 |
| 856 | 4 | 0 | |u https://www.jstor.org/stable/25436188 |3 Volltext |
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| 952 | |d 104 |j 2007 |e 28 |h 11736-11741 | ||