A genetically tractable model of human glioma formation.
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.
Rich
J N
JN
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. rich0001@mc.duke.edu
Guo
C
C
McLendon
R E
RE
Bigner
D D
DD
Wang
X F
XF
Counter
C M
CM
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D020134:Catalytic Domain; D002472:Cell Transformation, Viral / Q000235:genetics*; D004268:DNA-Binding Proteins; D011905:Genes, ras; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D012313:RNA; D012190:Retroviridae / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase