The requirement of p53 for maintaining chromosomal stability during tetraploidization

Tetraploidization is believed to promote genome instability and tumorigenesis. Whether tetraploids per se are intrinsically unstable and transforming remain incompletely understood. In this report, tetraploidization was induced with cell fusion using mouse fibroblasts. Due to the unequal segregation...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2010-11, Vol.1 (7), p.583-595
Main Authors: Ho, Chui Chui, Hau, Pok Man, Marxer, Miriam, Poon, Randy Y C
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Cell Culture Techniques
Cell Fusion
Cell Transformation, Neoplastic - drug effects
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - pathology
Cells, Cultured
Chromosomal Instability - drug effects
Chromosomal Instability - genetics
Chromosomal Instability - physiology
Gene Knockdown Techniques
Mice
Mice, Inbred C57BL
Mitosis - drug effects
Mitosis - genetics
Mitosis - physiology
Models, Biological
Research Papers
RNA, Small Interfering - pharmacology
Tetraploidy
Tumor Suppressor Protein p53 - antagonists & inhibitors
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tetraploidization is believed to promote genome instability and tumorigenesis. Whether tetraploids per se are intrinsically unstable and transforming remain incompletely understood. In this report, tetraploidization was induced with cell fusion using mouse fibroblasts. Due to the unequal segregation of chromosomes during multipolar mitosis, the majority of cells were eliminated by p53-dependent mechanisms after tetraploidization. The rare tetraploid fibroblasts that were able to undergo bipolar mitosis remained chromosomally stable and nontransformed over many generations. Suppression of p53 functions during tetraploidization, either by RNA interference or by using p53-deficient mouse fibroblasts, produced cells that were chromosomally unstable. They were fast growing and displayed anchorage-independent growth in soft agar. In contrast, impairment of p53 functions after tetraploids were established was ineffective in triggering chromosomal instability and transformation. Collectively, these results are consistent with a model that during early stages of tetraploidization, the lack of p53 promotes the survival of chromosomally unstable sub-tetraploids, leading to transformation. Once tetraploids are established, however, p53 is not essential for maintaining chromosome stability.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.193