Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/105889
Title: Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress.
Author: Domínguez, Daniel
Feijoo, Purificación
Bernal, Aina
Ercilla Eguiarte, Amaia
Agell i Jané, Neus
Genescà, Anna
Tusell, Laura
Keywords: Cèl·lules epitelials
Glàndules mamàries
Telòmer
Càncer
Biologia molecular
Epithelial cells
Mammary glands
Telomere
Cancer
Molecular biology
Issue Date: 29-Sep-2015
Publisher: Impact Journals
Abstract: Virtually all human cancers display chromosome instability (CIN), a condition in which chromosomes are gained or lost at a high rate. CIN occurs early in cancer development where it may undermine the advance of the neoplastic disease. With the aim of establishing the mechanisms underlying CIN in cancer, we investigated possible links between telomere-dysfunction and centrosome defects, which were seen to coincide in early in breast carcinogenesis using human mammary epithelial cells (HMECs). In this study, we show that TP53 proficient vHMECs cells develop centrosome aberrations when telomere-dysfunction genotoxic stress is produced in the presence of a defective p16INK4a setting and in parallel with an activation of the DNA damage checkpoint response. These aberrations consist of the accumulation of centrosomes in polyploid vHMECs, plus centriole overduplication in both diploid and polyploid cells, thus reflecting that distinct mechanisms underlie the generation of centrosome aberrations in vHMECs. Transduction of vHMEC with hTERT, which rescued the telomere dysfunction phenotype and consequently reduced DNA damage checkpoint activation, led to a progressive reduction of centrosome aberrations with cell culture, both in diploid and in polyploid vHMECs. Radiation-induced DNA damage also raised centrosome aberrations in vHMEC-hTERT. Collectively, our results, using vHMECs define a model where p16INK4a deficiency along with short dysfunctional telomeres cooperatively engenders centrosome abnormalities before p53 function is compromised.
Note: Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.4958
It is part of: Oncotarget, 2015, vol. 6, num. 29, p. 28238-28256
Related resource: https://doi.org/10.18632/oncotarget.4958
URI: http://hdl.handle.net/2445/105889
ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Biomedicina)

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