ArticleThe American journal of pathology2005
Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities.Neuroscience bulletin · 2023Review
- Review
- Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.Cancer research · 2015Article
- STAT3 Blockade Inhibits Radiation-Induced Malignant Progression in Glioma.Cancer research · 2015Article
- Differentiation of Glioma Stem Cells and Progenitor Cells into Local Host Cell-Like Cells: A Study Based on Choroidcarcinoma Differentiation of Choroid Plexus of GFP Transgenic Nude Mouse.Cancer biotherapy & radiopharmaceuticals · 2015Article
- Contemporary murine models in preclinical astrocytoma drug development.Neuro-oncology · 2015Review
- Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.Nature communications · 2014Article
- Anti-tumor effect of a novel PI3-kinase inhibitor, SF1126, in (12) V-Ha-Ras transgenic mouse glioma model.Cancer cell international · 2014Article
- Glial progenitors as targets for transformation in glioma.Advances in cancer research · 2014Review
- What underlies the diversity of brain tumors?Cancer metastasis reviews · 2013Review
- Transcriptional analysis of aggressiveness and heterogeneity across grades of astrocytomas.PloS one · 2013Article
- Targeting Tregs in Malignant Brain Cancer: Overcoming IDO.Frontiers in immunology · 2013Article
- Review: insights gained from modelling high-grade glioma in the mouse.Neuropathology and applied neurobiology · 2012Review
- Article
- Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors.Neuro-oncology · 2011Article
- Invasion precedes tumor mass formation in a malignant brain tumor model of genetically modified neural stem cells.Neoplasia (New York, N.Y.) · 2011Article
- Mouse models to interrogate the implications of the differentiation status in the ontogeny of gliomas.Oncotarget · 2011Review
- Review
- A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas.The Journal of experimental medicine · 2011Article
- Targeting Ras-RAF-ERK and its interactive pathways as a novel therapy for malignant gliomas.Current cancer drug targets · 2010Review
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Authors and funding
6 authors.
Funding
Abstract
We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocyte-specific, activated (12)V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low- and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring low- or high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp 53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of (12)V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.
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