RGD Reference Report - GFAP-Cre-mediated activation of oncogenic K-ras results in expansion of the subventricular zone and infiltrating glioma. - Rat Genome Database

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GFAP-Cre-mediated activation of oncogenic K-ras results in expansion of the subventricular zone and infiltrating glioma.

Authors: Abel, Ty W  Clark, Cara  Bierie, Brian  Chytil, Anna  Aakre, Mary  Gorska, Agnieszka  Moses, Harold L 
Citation: Abel TW, etal., Mol Cancer Res. 2009 May;7(5):645-53. doi: 10.1158/1541-7786.MCR-08-0477. Epub 2009 May 12.
RGD ID: 13702860
Pubmed: PMID:19435821   (View Abstract at PubMed)
PMCID: PMC3406747   (View Article at PubMed Central)
DOI: DOI:10.1158/1541-7786.MCR-08-0477   (Journal Full-text)

A subset of neoplastic cells within human high-grade gliomas has features associated with stem cells. These cells may sustain glioma growth, and their stem-like properties may confer resistance to standard glioma treatments. Whether glioma stem cells derive from indigenous neural stem cells (NSC), or from tumor cells that have reacquired stem cell-like properties, is unknown. However, signaling pathways that are tightly regulated and central to NSC biology, including the Ras/Raf/Erk pathway, are hyperactive and pathogenic in gliomagenesis. Furthermore, data in animal models suggests that, in some cases, tumors are initiated in the subventricular zone (SVZ), a stem/progenitor cell niche in the mature brain. We activated oncogenic K-ras in mouse glioneuronal precursor cells and adult SVZ cells using GFAP-Cre. GFAP-Cre+/K-ras(G12D) mice showed a marked expansion of glial fibriallary acidic protein (GFAP)- and TUJ1-expressing cell populations in the SVZ. In addition, mice developed intermediate grade, infiltrating glioma with 100% penetrance. Tumors were consistently located in the amygdalohippocampal region and nearby cortex, often in association with the lateral ventricle and expanded SVZ. Tumor cells expressed markers associated with neural progenitor cells, including Olig2, Bmi-1, and PDGFR-alpha. These data suggest that infiltrating tumor cells may arise from NSC transformed by activation of oncogenic K-ras in vivo.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KRASHumanhigh grade glioma severityISOKras (Mus musculus) RGD 
KrasRathigh grade glioma severityISOKras (Mus musculus) RGD 
KrasMousehigh grade glioma severityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kras  (KRAS proto-oncogene, GTPase)

Genes (Mus musculus)
Kras  (Kirsten rat sarcoma viral oncogene homolog)

Genes (Homo sapiens)
KRAS  (KRAS proto-oncogene, GTPase)


Additional Information