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 language | English |
|---|---|
| Pages (from-to) | 1380-1385 |
| Number of pages | 6 |
| Journal | Cell Cycle |
| Volume | 8 |
| Issue number | 9 |
| Publication status | Published - May 1 2009 |
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Keywords
- Cancer
- Chemoresistance
- Cytochalasin D
- Dihydrocytochalasin B
- Mitochondrial outer membrane permeabilization
- Mitoxantrone
- Nocodazole
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Developmental Biology
Cite this
p53 represses the polyploidization of primary mammary epithelial cells by activating apoptosis. / Senovilla, Laura; Vitale, Ilio; Galluzzi, Lorenzo; Vivet, Sonia; Joza, Nicholas; Younes, Amena Ben; Rello-Varona, Santiago; Castedo, Maria; Kroemer, Guido.
In: Cell Cycle, Vol. 8, No. 9, 01.05.2009, p. 1380-1385.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - p53 represses the polyploidization of primary mammary epithelial cells by activating apoptosis
AU - Senovilla, Laura
AU - Vitale, Ilio
AU - Galluzzi, Lorenzo
AU - Vivet, Sonia
AU - Joza, Nicholas
AU - Younes, Amena Ben
AU - Rello-Varona, Santiago
AU - Castedo, Maria
AU - Kroemer, Guido
PY - 2009/5/1
Y1 - 2009/5/1
N2 - 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.
AB - 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.
KW - Cancer
KW - Chemoresistance
KW - Cytochalasin D
KW - Dihydrocytochalasin B
KW - Mitochondrial outer membrane permeabilization
KW - Mitoxantrone
KW - Nocodazole
UR - http://www.scopus.com/inward/record.url?scp=65949111063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65949111063&partnerID=8YFLogxK
M3 - Article
VL - 8
SP - 1380
EP - 1385
JO - Cell Cycle
JF - Cell Cycle
SN - 1538-4101
IS - 9
ER -