Centrosome aberrations in human mammary epithelial cells driven by cooperative interactions between p16INK4a deficiency and telomere-dependent genotoxic stress

Oncotarget
Daniel DomínguezLaura Tusell

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...Continue Reading

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Citations

Dec 15, 2017·Journal of Cellular Physiology·Mahdi RivandiAmir Avan
Mar 1, 2017·Journal of Proteome Research·Anna DrabikMarek Sierzega

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Methods Mentioned

BETA
immunoFISH
FACS
Fluorescence Imaging

Software Mentioned

Genus
Cytovision
Isis Fluorescence Imaging
SPSS
BDFacsDiva
Fiji

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