In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice

Détails

ID Serval
serval:BIB_0B67D230FD26
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice
Périodique
Oncogene
Auteur⸱e⸱s
Harvey  M., Sands  A. T., Weiss  R. S., Hegi  M. E., Wiseman  R. W., Pantazis  P., Giovanella  B. C., Tainsky  M. A., Bradley  A., Donehower  L. A.
ISSN
0950-9232 (Print)
Statut éditorial
Publié
Date de publication
09/1993
Volume
8
Numéro
9
Pages
2457-67
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep
Résumé
Fibroblast cultures were derived from mouse embryos containing either one (p53+/-) or two (p53-/-) inactivated p53 alleles and compared to normal embryo fibroblasts for a number of growth parameters. Early passage p53-deficient embryo fibroblasts (p53-/-) divided faster than normal embryo fibroblasts, achieved higher confluent densities, and had a higher fraction of division-competent cells under conditions of low cell density. Flow cytometry studies of early passage embryo fibroblasts showed that the percent of p53-deficient cells in G0/G1 was lower than in normal cells, consistent with the argument that p53 mediates a G1 block. When p53-deficient and normal cells were passaged for long periods of time, the homozygote (p53-/-) fibroblasts grew at a high rate for over 50 passages and never entered a non-growing senescent phase characteristic of the heterozygote (p53+/-) and normal (p53+/+) cells. The p53-deficient fibroblasts were genetically unstable during passaging, with the p53-/- cells showing a high degree of aneuploidy and the p53+/- cells displaying a moderate level of chromosomal abnormalities by passage 25. Surprisingly, the heterozygote cells lost their single wild type allele very early during culturing and in spite of this loss most heterozygote lines entered into senescence. We conclude that the loss of p53 by itself is insufficient to confer immortality on a cell, but does confer a growth advantage. Taken together, the findings confirm that the absence of p53 promotes genomic instability, which in turn may result in genetic alterations which directly produce immortality.
Mots-clé
Animals Base Sequence *Cell Cycle Creatine Kinase/genetics Fibroblasts/cytology Gene Expression *Genes, p53 Karyotyping Mice/embryology Molecular Sequence Data Nuclear Proteins/genetics Oligodeoxyribonucleotides/chemistry Proliferating Cell Nuclear Antigen RNA, Messenger/genetics Tumor Suppressor Protein p53/*deficiency
Pubmed
Web of science
Création de la notice
25/01/2008 14:06
Dernière modification de la notice
20/08/2019 13:33
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