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150325s2009 xx |||||o 00| ||eng c |
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|a (DE-627)JST069859957
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|a (JST)40484963
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|a DE-627
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|c DE-627
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|a eng
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|a Moore, Lynette M.
|e verfasserin
|4 aut
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|a IGFBP2 Is a Candidate Biomarker for Ink4a-Arf Status and a Therapeutic Target for High-Grade Gliomas
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|c 2009
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|a Text
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|a Computermedien
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|a The levels of insulin-like growth factor-binding protein 2 (IGFBP2) are elevated during progression of many human cancers. By using a glial-specific transgenic mouse system (RCAS/Ntv-a), we reported previously that IGFBP2 is an oncogenic factor for glioma progression in combination with platelet-derived growth factor-β (PDGFB). Because the INK4a-ARF locus is often deleted in highgrade gliomas (anaplastic oligodendroglioma and glioblastoma), we investigated the effect of the lnk4a-Arf-null background on IGFBP2-mediated progression of PDGFB-initiated oligodendroglioma. We demonstrate here that homozygous deletion of Ink4a-Arf bypasses the requirement of exogenously introduced IGFBP2 for glioma progression. Instead, absence of Ink4a-Arf resulted in elevated endogenous tumor cell IGFBP2. An inverse relationship between $p16^{INK4a} $ and IGFBP2 expression was also observed in human glioma tissue samples and in 90 different cancer cell lines by using Western blotting and reverse-phase protein lysate arrays. When endogenous IGFBP2 expression was attenuated by an RCAS vector expressing antisense IGFBP2 in our mouse model, a decreased incidence of anaplastic oligodendroglioma as well as prolonged survival was observed. Thus, $p16^{INK4a} $ is a negative regulator of the IGFBP2 oncogene. Loss of Ink4a-Arf results in increased IGFBP2, which contributes to glioma progression, thereby implicating IGFBP2 as a marker and potential therapeutic target for lnk4a-Arf-deleted gliomas.
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Tumors
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Germ cell and embryonal neoplasms
|x Glioma
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Cancer
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Zoology
|x Animals
|x Mammals
|x Rodents
|x Mice
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Germ cell and embryonal neoplasms
|x Glioma
|x Oligodendroglioma
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Cytology
|x Cell biology
|x Cells
|x Cultured cells
|x Cell lines
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Cytology
|x Cell biology
|x Cells
|x Stem cells
|x Progenitor cells
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Genetics
|x Medical genetics
|x Human genetics
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Germ cell and embryonal neoplasms
|x Glioma
|x Astrocytoma
|x Glioblastoma
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| 650 |
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|a Health sciences
|x Medical treatment
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Tumors
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Germ cell and embryonal neoplasms
|x Glioma
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Cancer
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Zoology
|x Animals
|x Mammals
|x Rodents
|x Mice
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| 650 |
|
4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Germ cell and embryonal neoplasms
|x Glioma
|x Oligodendroglioma
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Cytology
|x Cell biology
|x Cells
|x Cultured cells
|x Cell lines
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Cytology
|x Cell biology
|x Cells
|x Stem cells
|x Progenitor cells
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| 650 |
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4 |
|a Biological sciences
|x Biology
|x Genetics
|x Medical genetics
|x Human genetics
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| 650 |
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4 |
|a Health sciences
|x Medical conditions
|x Diseases
|x Neoplasia
|x Germ cell and embryonal neoplasms
|x Glioma
|x Astrocytoma
|x Glioblastoma
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| 650 |
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4 |
|a Health sciences
|x Medical treatment
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| 655 |
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|a research-article
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1 |
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|a Holmes, Kristen M.
|e verfasserin
|4 aut
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|a Smith, Sarah M.
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wu, Ying
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Tchougounova, Elena
|e verfasserin
|4 aut
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| 700 |
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|a Uhrbom, Lene
|e verfasserin
|4 aut
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| 700 |
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|a Sawaya, Raymond
|e verfasserin
|4 aut
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|a Bruner, Janet M.
|e verfasserin
|4 aut
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|a Fuller, Gregory N.
|e verfasserin
|4 aut
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| 700 |
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|a Zhang, Wei
|e verfasserin
|4 aut
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| 700 |
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|a Cavenee, Webster K.
|e verfasserin
|4 aut
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| 773 |
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|g volume:106
|g year:2009
|g number:39
|g pages:16675-16679
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|u https://www.jstor.org/stable/40484963
|3 Volltext
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|d 106
|j 2009
|e 39
|h 16675-16679
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