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HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes

Cell adhesion plays an important role in neoplastic transformation. Thus, anchorage-independent growth and epithelial-mesenchymal transition, which are features associated to anoikis-resistance, are vital steps in cancer progression and metastatic colonization. Cell attachment loss may induce intrac...

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Autores principales: da Silva, Rodrigo A., Sammartino Mariano, Flavia, Planello, Aline. C., Line, Sergio R.P., de Souza, Ana Paula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668640/
https://www.ncbi.nlm.nih.gov/pubmed/29124149
http://dx.doi.org/10.1016/j.bbrep.2015.05.008
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author da Silva, Rodrigo A.
Sammartino Mariano, Flavia
Planello, Aline. C.
Line, Sergio R.P.
de Souza, Ana Paula
author_facet da Silva, Rodrigo A.
Sammartino Mariano, Flavia
Planello, Aline. C.
Line, Sergio R.P.
de Souza, Ana Paula
author_sort da Silva, Rodrigo A.
collection PubMed
description Cell adhesion plays an important role in neoplastic transformation. Thus, anchorage-independent growth and epithelial-mesenchymal transition, which are features associated to anoikis-resistance, are vital steps in cancer progression and metastatic colonization. Cell attachment loss may induce intracellular oxidative stress, which triggers DNA damage as methylation changes. HaCaT lineage cells were submitted to periods of 1, 3, 5 and 24 h of anchorage blockage with the purpose of study of oxidative stress effect on changes in the DNA methylation pattern, derived from attachment blockade. Through this study, HaCaT anchorage blockage-induced oxidative stress was reported to mediate alterations in global DNA methylation changes and into TP53 gene promoter pattern during anoikis-resistance acquisition. Furthermore, at the first experimental time-periods (1, 3 and 5 h), genome hypermethylation was found; however, genome hypomethylation was observed in later time-periods (24 h) of attachment impediment. The TP 53 methylation analyses were performed after 24 h of replated anoikis-resistance cells and same methylation pattern was observed, occurring an early (1 and 3 h) hypermethylation that was followed by late (5 and 24 h) hypomethylation. However, LINE-1, a marker of genomic instability, was perceived in time-dependent hypomethylation. The mRNA levels of the DNMTs enzymes were influenced by cell attachment blockage, but non-conclusive results were obtained in order to match DNMTs transcription to pattern methylation results. In conclusion, DNA damage was found, leaded by oxidative stress that has come up from HaCaT anchorage blockade, which rises a global genome hypomethylation tendency as consequence, which might denote genomic instability.
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spelling pubmed-56686402017-11-09 HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes da Silva, Rodrigo A. Sammartino Mariano, Flavia Planello, Aline. C. Line, Sergio R.P. de Souza, Ana Paula Biochem Biophys Rep Research Article Cell adhesion plays an important role in neoplastic transformation. Thus, anchorage-independent growth and epithelial-mesenchymal transition, which are features associated to anoikis-resistance, are vital steps in cancer progression and metastatic colonization. Cell attachment loss may induce intracellular oxidative stress, which triggers DNA damage as methylation changes. HaCaT lineage cells were submitted to periods of 1, 3, 5 and 24 h of anchorage blockage with the purpose of study of oxidative stress effect on changes in the DNA methylation pattern, derived from attachment blockade. Through this study, HaCaT anchorage blockage-induced oxidative stress was reported to mediate alterations in global DNA methylation changes and into TP53 gene promoter pattern during anoikis-resistance acquisition. Furthermore, at the first experimental time-periods (1, 3 and 5 h), genome hypermethylation was found; however, genome hypomethylation was observed in later time-periods (24 h) of attachment impediment. The TP 53 methylation analyses were performed after 24 h of replated anoikis-resistance cells and same methylation pattern was observed, occurring an early (1 and 3 h) hypermethylation that was followed by late (5 and 24 h) hypomethylation. However, LINE-1, a marker of genomic instability, was perceived in time-dependent hypomethylation. The mRNA levels of the DNMTs enzymes were influenced by cell attachment blockage, but non-conclusive results were obtained in order to match DNMTs transcription to pattern methylation results. In conclusion, DNA damage was found, leaded by oxidative stress that has come up from HaCaT anchorage blockade, which rises a global genome hypomethylation tendency as consequence, which might denote genomic instability. Elsevier 2015-05-30 /pmc/articles/PMC5668640/ /pubmed/29124149 http://dx.doi.org/10.1016/j.bbrep.2015.05.008 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
da Silva, Rodrigo A.
Sammartino Mariano, Flavia
Planello, Aline. C.
Line, Sergio R.P.
de Souza, Ana Paula
HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes
title HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes
title_full HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes
title_fullStr HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes
title_full_unstemmed HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes
title_short HaCaT anchorage blockade leads to oxidative stress, DNA damage and DNA methylation changes
title_sort hacat anchorage blockade leads to oxidative stress, dna damage and dna methylation changes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668640/
https://www.ncbi.nlm.nih.gov/pubmed/29124149
http://dx.doi.org/10.1016/j.bbrep.2015.05.008
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