ArticlePloS one2010
The ability to generate senescent progeny as a mechanism underlying breast cancer cell heterogeneity.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Analysis of terminal duct lobular unit involution in luminal A and basal breast cancers.Breast cancer research : BCR · 2012Trial
- New Mitochondria-Targeted Fisetin Derivative Compromises Mitophagy and Limits Survival of Drug-Induced Senescent Breast Cancer Cells.Journal of medicinal chemistry · 2024Article
- Fibroblast heterogeneity and functions: insights from single-cell sequencing in wound healing, breast cancer, ovarian cancer and melanoma.Frontiers in genetics · 2024Review
- TRIM27 Functions as a Novel Oncogene in Non-Triple-Negative Breast Cancer by Blocking Cellular Senescence through p21 Ubiquitination.Molecular therapy. Nucleic acids · 2020Article
- Senescence-Associated Pro-inflammatory Cytokines and Tumor Cell Plasticity.Frontiers in molecular biosciences · 2020Review
- SNHG6 is upregulated in primary breast cancers and promotes cell cycle progression in breast cancer-derived cell lines.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- Senescence-associated IL-6 and IL-8 cytokines induce a self- and cross-reinforced senescence/inflammatory milieu strengthening tumorigenic capabilities in the MCF-7 breast cancer cell line.Cell communication and signaling : CCS · 2017Article
- Estrogen receptor alpha inhibits senescence-like phenotype and facilitates transformation induced by oncogenic ras in human mammary epithelial cells.Oncotarget · 2016Article
- Retinoids induce cellular senescence in breast cancer cells by RAR-β dependent and independent pathways: Potential clinical implications (Review).International journal of oncology · 2015Review
- Immortalised breast epithelia survive prolonged DNA replication stress and return to cycle from a senescent-like state.Cell death & disease · 2014Article
- Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor-α.BMC cancer · 2012Article
- Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence.International journal of cancer · 2012Article
- A p53-independent role of Mdm2 in estrogen-mediated activation of breast cancer cell proliferation.Breast cancer research : BCR · 2011Article
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Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBreast cancer is a remarkably heterogeneous disease. Luminal, basal-like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity. METHODOLOGY/PRINCIPAL
findingsA panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP) and immortal cell progenitor (ICP) subtypes. All SCP cell lines expressed estrogen receptor (ER). Loss of ER expression combined with the accumulation of p21(Cip1) correlated with senescence in these cell lines. p21(Cip1) knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24-/ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal-like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and "normal-like" tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice. CONCLUSIONS/SIGNIFICANCE: Luminal A and "normal-like" breast cancer cell lines were able to generate luminal-like and myoepithelial-like progeny undergoing senescence arrest. In contrast, luminal B/basal-like cell lines acted as stem/progenitor cells with defective differentiation capacities. Our findings suggest that the malignancy of breast tumors is directly correlated with stem/progenitor phenotypes and poor differentiation potential.
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