A genetically tractable model of human glioma formation.
PubMedPublished 1 May 2001
Jeremy N. Rich, Congting Guo, Roger E. McLendon, Darell D. Bigner, Xiao‐Fan Wang, Christopher M. Counter
Citations140
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TL;DR
This model system will, for the first time, allow the biological significance of selected genetic alterations to be studied in human gliomas and were tumorigenic with pathology consistent with grade III-IV neuroectodermal tumors in mice.
Abstract
Gliomas remain one of the deadliest forms of cancer. Improved therapeutics will require a better understanding of the molecular nature of these tumors. We, therefore, mimicked the most common genetic changes found in grade III-IV gliomas, disruption of the p53 and RB pathways and activation of telomere maintenance and independence from growth factors, through the ectopic expression of the SV40 T/t-Ag oncogene, an oncogenic form of H-ras (H-ras(V12G)), and the human telomerase catalytic subunit hTERT in normal human astrocytes. The resulting cells displayed many of the hallmarks of grade III-IV gliomas, including greatly expanded life span and growth in soft agar and, most importantly, were tumorigenic with pathology consistent with grade III-IV neuroectodermal tumors in mice. This model system will, for the first time, allow the biological significance of selected genetic alterations to be studied in human gliomas.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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