Loss of one but not two mdm2 null alleles alters the tumour spectrum in p53 null mice

Citation
Tj. Mcdonnell et al., Loss of one but not two mdm2 null alleles alters the tumour spectrum in p53 null mice, J PATHOLOGY, 188(3), 1999, pp. 322-328
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
JOURNAL OF PATHOLOGY
ISSN journal
0022-3417 → ACNP
Volume
188
Issue
3
Year of publication
1999
Pages
322 - 328
Database
ISI
SICI code
0022-3417(199907)188:3<322:LOOBNT>2.0.ZU;2-U
Abstract
The transcriptional activity of the p53 tumour suppressor is inhibited by b inding to MDM2. The in vivo significance of this interaction was establishe d in mdm2 null mice. Embryonic lethality due to loss of mdm2 is completely rescued by deletion of p53, indicating that the lethality is due to inabili ty to down-modulate p53 function, The production of mice null for both p53 and mdm2 led to an assessment of the role of MDM2 in tumour development, Tu mour latency and spectrum in p53 null mice were monitored in the presence o r absence of mdm2. Tno unusual findings resulted: tumour latency. in p53 nu ll/mdm2 heterozygous mice nas longer than in p53/mdm2 double-null mice; and the incidence of sarcomas was higher in p53 null/mdm2 heterozygous mice th an in p53 null or p53/mdm2 double-null mice. These data raise the possibili ty that heterozygosity at the mdm2 locus in the absence of p53 affects the development of tumours of mesenchymal origin. (C) 1999 John Wiley & Sons, L td.