Mechanisms of glioma genesis in P53 knock-out mice

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 11671386
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Saitama Medical University
• Principal Investigator: NISHIKAWA Ryo Saitama Medical School, School of medicine, Associate professor, 医学部, 助教授 (90237678)
• Project Period (FY): 1999 – 2000
• Keywords: glioma / p53 / knockout mouse

Research Abstract

We administered 25mg/kg to 75mg/kg ethylnitrosourea to pregnant p53(+/-) knockout mice intraperitoneally, and obtained 73 p53(+/+), 80 p53(+/-) and ten p53(-1-) pops, Among them, three p53(+/-) (#370, #400, #505) and one p53(-/-) mice (#537) developed intracranial tumors at around ten weeks (#370 and #537) and 30 weeks (#400 and #505) from birth
All of the four tumors were immunoreactive to GFAP antibody and showed high labeling indices for PCNA, which indicated their gilal origin. Tumors at earlier onset showed less differentiated features. Nestin, a stem cell marker, was expressed in a tumor #537 that was p53(-/-). NeuN, a neuronal marker, was expressed in tumors #370 and #537, two of the earlier onset tumors. An oligodendroglial marker, CNPase, was negative in all the tumors. Apoptotic cells, expressions of Bax. Bcl-2, FAS, and cyclinA were negative in all the tumors as well as non-tumorous brains. Thrombospondin expression was observed only in small vessels of non-ttunorous brain no matter what the p53 genotype was
ENU-induced glial tumors in p53 knockout mice, especially those of p53(-/-) genotype, were suggested to originate from stem cells, as they showed Nestin expression and neuronal cell phenotype. Tumors of late onset lost those stem cell phenotypes