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

Laura Senovilla, Ilio Vitale, Lorenzo Galluzzi, Sonia Vivet, Nicholas Joza, Amena Ben Younes, Santiago Rello-Varona, Maria Castedo, Guido Kroemer

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1380-1385
Number of pages6
JournalCell Cycle
Volume8
Issue number9
Publication statusPublished - May 1 2009

Keywords

  • Cancer
  • Chemoresistance
  • Cytochalasin D
  • Dihydrocytochalasin B
  • Mitochondrial outer membrane permeabilization
  • Mitoxantrone
  • Nocodazole

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Senovilla, L., Vitale, I., Galluzzi, L., Vivet, S., Joza, N., Younes, A. B., Rello-Varona, S., Castedo, M., & Kroemer, G. (2009). p53 represses the polyploidization of primary mammary epithelial cells by activating apoptosis. Cell Cycle, 8(9), 1380-1385.