p53 represses the polyploidization of primary mammary epithelial cells by activating apoptosis.

Abstract

Tetraploidy may constitute a metastable state leading to numeric and structural chromosome abnormalities that are associated with cancer. Here, we show that cultured primary p53(-/-) (but not wild type, WT) mouse mammary epithelial cells (MMECs) accumulate a tetraploid sub-population in vitro. This occurs spontaneously, yet can be exacerbated by the addition of microtubule inhibitors as well as of inhibitors of cytokinesis. As compared to WT cells, tetraploid p53(-/-) MMECs contain supernumerary centrosomes and exhibit a reduced propensity to initiate the mitochondrial pathway of apoptosis. Moreover, tetraploid p53(-/-) MMECs are more resistant against anthracyclin-induced cell killing than their diploid counterparts. Altogether, these data indicate that p53 normally suppresses the generation of tetraploid cells, presumably by activating the intrinsic pathway of apoptosis. In the absence of p53, tetraploid cells accumulate as a result of inhibited apoptosis, which contributes to the acquisition of chemotherapy resistance.

• Authors: Laura Senovilla, Ilio Vitale, Lorenzo Galluzzi, Sonia Vivet, Nicholas Joza, Amena Ben Younes, Santiago Rello-Varona, Maria Castedo, Guido Kroemer
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 8 Issue 9 Pg. 1380-5 (May 01 2009) ISSN: 1551-4005 [Electronic] United States
• PMID: 19342895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Suppressor Protein p53

Topics

• Animals
• Apoptosis
• Cell Death
• Cell Lineage
• Cells, Cultured
• Centrosome (metabolism)
• Epithelial Cells (cytology, metabolism)
• Mammary Glands, Animal (cytology)
• Mice
• Mice, Inbred C57BL
• Polyploidy
• Tumor Suppressor Protein p53 (metabolism)