Reduced latency but no increased brain tumor penetrance in mice with astrocyte specific expression of a human p53 mutant
Details
Serval ID
serval:BIB_561595A7227E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Reduced latency but no increased brain tumor penetrance in mice with astrocyte specific expression of a human p53 mutant
Journal
Oncogene
ISSN
0950-9232 (Print)
Publication state
Published
Issued date
11/2000
Volume
19
Number
47
Pages
5329-37
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 9
Research Support, Non-U.S. Gov't --- Old month value: Nov 9
Abstract
p53-germline mutations located in the core DNA-binding domain have been associated with a more dominant tumor penetrance especially for breast cancer and brain tumors. We previously reported an unusual accumulation of CNS tumors associated with a unique p53 germline mutation, Y236delta (deletion of codon 236). To test whether this tissue-specific tumor predisposition reflects a gain-of-function activity of Y236delta, we generated transgenic mice expressing Y236delta in astrocytes using the regulatory elements of the glial fibrillary acidic protein (GFAP) gene. After transplacental exposure to N-ethyl-N-nitrosourea (25 mg/kg BW) brain tumors developed in 18% (7/39) of GFAP-Y236delta transgenic p53-/- mice, while in p53+/- mice the incidence was 28% (11/40) (P>0.3). However, the mean tumor latency for GFAP-Y236delta/p53+/- mice was significantly shorter than for p53+/- mice, with 19.9 weeks vs 31.6 weeks (P=0.039), respectively. Taken together, cell specific expression of Y236delta results in an acceleration of tumor progression but does not confer a higher tumor penetrance. Conceivably, the transdominant effect of Y236delta provided a growth advantage early in the progression of neoplastic cells, since the endogenous p53 wild-type allele was lost in all brain tumors independent of the genotype. This reflects well observations from human astrocytic neoplasms with p53 mutations.
Keywords
Animals
Astrocytes/*metabolism
Astrocytoma/classification/metabolism/pathology
Brain Neoplasms/classification/metabolism/*pathology
Female
Gene Expression
Germ-Line Mutation
Glioblastoma/classification/metabolism/pathology
Glioma/classification/metabolism/*pathology
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Microsatellite Repeats
Neoplasm Invasiveness
Telencephalon
Tumor Suppressor Protein p53/genetics/metabolism/*physiology
Pubmed
Web of science
Create date
25/01/2008 13:06
Last modification date
20/08/2019 14:10