Global DNA Hypomethylation following 5-aza-2'-deoxycytidine treatment induces aneuploidy in HCT-116 tumor cells.

Risultato della ricerca: Other

Abstract

Aneuploidy, the alteration of the normal number of chromosomes, is found in most of the human solidtumors and correlated with to defects in the process of chromosome segregation (1). It was also suggestedthat the alteration of the 5-methylcytosine (5-mC) pattern in the chromosome pericentromeric region,generated to aneuploid cells (2, 3). To investigate the relationship between hypomethylation and wholechromosome aneuploidy, we treated HCT-116 cells, a near diploid line, with the demethylating agent 5-aza-2'-deoxycytidine (DAC). The treatment with DAC for 24, 48 and 72 hours produced a progressive reductionof DNA methylation as shown by decrease of 5-mC signal. DNA hypomethylation resulted in a strongchange of 5-mC distribution pattern in metaphase chromosomes that was associated with severalchromosome abnormalities, such as: highly hypocondensed chromosomes, "rail-road track" chromosomesand endoreduplication. Live imaging experiments of HCT-116 cells expressing H2B-GFP and DAC treated,showed misaligned and lagging chromosomes, micronuclei, and elongation of metaphase-anaphasetransition. All together these results provide further strong evidence of the correlation between DNAhypomethylation and aneuploidy in human somatic cells.References1. H. Rajagopalan, C. Lengauer, Aneuploidy and cancer. Nature 432, 338 (Nov 18, 2004).2. D. Prada et al., Satellite 2 demethylation induced by 5-azacytidine is associated with missegregationof chromosomes 1 and 16 in human somatic cells. Mutat.Res. 729, 100 (2012).3. L. A. Herrera, D. Prada, M. A. Andonegui, A. Duenas-Gonzalez, The epigenetic origin ofaneuploidy. Curr.Genomics 9, 43 (2008)
Lingua originaleEnglish
Numero di pagine48
Stato di pubblicazionePublished - 2013

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