title: 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.affiliation: INSERM, U848, and Institut Gustave Roussy, and Université Paris Sud-XI, 11, Villejuif, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Senovilla
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Sonia
authors.initials: S
authors.lastname: Vivet
authors.forename: Nicholas
authors.initials: N
authors.lastname: Joza
authors.forename: Amena Ben
authors.initials: AB
authors.lastname: Younes
authors.forename: Santiago
authors.initials: S
authors.lastname: Rello-Varona
authors.forename: Maria
authors.initials: M
authors.lastname: Castedo
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer