A genetically tractable model of human glioma formation.

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.

• Authors: J N Rich, C Guo, R E McLendon, D D Bigner, X F Wang, C M Counter
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 9 Pg. 3556-60 (May 01 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11325817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Polyomavirus Transforming
• DNA-Binding Proteins
• telomerase RNA
• RNA
• Telomerase

Topics

• Animals
• Antigens, Polyomavirus Transforming (biosynthesis, genetics)
• Astrocytes (metabolism, pathology, physiology)
• Catalytic Domain
• Cell Transformation, Viral (genetics)
• DNA-Binding Proteins
• Genes, ras
• Glioma (genetics, pathology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Mice, SCID
• RNA
• Retroviridae (genetics)
• Telomerase (biosynthesis, genetics)
• Tumor Cells, Cultured