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

Details

Serval ID
serval:BIB_0B67D230FD26
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In vitro growth characteristics of embryo fibroblasts isolated from p53-deficient mice
Journal
Oncogene
Author(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)
Publication state
Published
Issued date
09/1993
Volume
8
Number
9
Pages
2457-67
Notes
Journal Article
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep
Abstract
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.
Keywords
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
Create date
25/01/2008 13:06
Last modification date
20/08/2019 12:33
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