High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.

Acquired drug resistance represents a frequent obstacle which hampers efficient chemotherapy of cancers. The contribution of aberrant DNA methylation to the development of drug resistant tumor cells has gained increasing attention over the past decades. Hence, the objective of the presented study wa...

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Autores principales:	Michael Boettcher, Frank Kischkel, Jörg D Hoheisel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95f8873783c34a0eacea5496ce3540d7
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spelling	oai:doaj.org-article:95f8873783c34a0eacea5496ce3540d72021-12-02T20:21:06ZHigh-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.1932-620310.1371/journal.pone.0011002https://doaj.org/article/95f8873783c34a0eacea5496ce3540d72010-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20544021/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Acquired drug resistance represents a frequent obstacle which hampers efficient chemotherapy of cancers. The contribution of aberrant DNA methylation to the development of drug resistant tumor cells has gained increasing attention over the past decades. Hence, the objective of the presented study was to characterize DNA methylation changes which arise from treatment of tumor cells with the chemotherapeutic drug doxorubicin. DNA methylation levels from CpG islands (CGIs) linked to twenty-eight genes, whose expression levels had previously been shown to contribute to resistance against DNA double strand break inducing drugs or tumor progression in different cancer types were analyzed. High-definition DNA methylation profiles which consisted of methylation levels from 800 CpG sites mapping to CGIs around the transcription start sites of the selected genes were determined. In order to investigate the influence of CGI methylation on the expression of associated genes, their mRNA levels were investigated via qRT-PCR. It was shown that the employed method is suitable for providing highly accurate methylation profiles, comparable to those obtained via clone sequencing, the gold standard for high-definition DNA methylation studies. In breast carcinoma cells with acquired resistance against the double strand break inducing drug doxorubicin, changes in methylation of specific cytosines from CGIs linked to thirteen genes were detected. Moreover, similarities between methylation profiles obtained from breast and ovarian carcinoma cell lines with acquired doxorubicin resistance were found. The expression levels of a subset of analyzed genes were shown to be linked to the methylation levels of the analyzed CGIs. Our results provide detailed DNA methylation information from two separate model systems for acquired doxorubicin resistance and suggest the occurrence of similar methylation changes in both systems upon exposure to the drug.Michael BoettcherFrank KischkelJörg D HoheiselPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 6, p e11002 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael Boettcher Frank Kischkel Jörg D Hoheisel High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.
description	Acquired drug resistance represents a frequent obstacle which hampers efficient chemotherapy of cancers. The contribution of aberrant DNA methylation to the development of drug resistant tumor cells has gained increasing attention over the past decades. Hence, the objective of the presented study was to characterize DNA methylation changes which arise from treatment of tumor cells with the chemotherapeutic drug doxorubicin. DNA methylation levels from CpG islands (CGIs) linked to twenty-eight genes, whose expression levels had previously been shown to contribute to resistance against DNA double strand break inducing drugs or tumor progression in different cancer types were analyzed. High-definition DNA methylation profiles which consisted of methylation levels from 800 CpG sites mapping to CGIs around the transcription start sites of the selected genes were determined. In order to investigate the influence of CGI methylation on the expression of associated genes, their mRNA levels were investigated via qRT-PCR. It was shown that the employed method is suitable for providing highly accurate methylation profiles, comparable to those obtained via clone sequencing, the gold standard for high-definition DNA methylation studies. In breast carcinoma cells with acquired resistance against the double strand break inducing drug doxorubicin, changes in methylation of specific cytosines from CGIs linked to thirteen genes were detected. Moreover, similarities between methylation profiles obtained from breast and ovarian carcinoma cell lines with acquired doxorubicin resistance were found. The expression levels of a subset of analyzed genes were shown to be linked to the methylation levels of the analyzed CGIs. Our results provide detailed DNA methylation information from two separate model systems for acquired doxorubicin resistance and suggest the occurrence of similar methylation changes in both systems upon exposure to the drug.
format	article
author	Michael Boettcher Frank Kischkel Jörg D Hoheisel
author_facet	Michael Boettcher Frank Kischkel Jörg D Hoheisel
author_sort	Michael Boettcher
title	High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.
title_short	High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.
title_full	High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.
title_fullStr	High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.
title_full_unstemmed	High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.
title_sort	high-definition dna methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/95f8873783c34a0eacea5496ce3540d7
work_keys_str_mv	AT michaelboettcher highdefinitiondnamethylationprofilesfrombreastandovariancarcinomacelllineswithdifferingdoxorubicinresistance AT frankkischkel highdefinitiondnamethylationprofilesfrombreastandovariancarcinomacelllineswithdifferingdoxorubicinresistance AT jorgdhoheisel highdefinitiondnamethylationprofilesfrombreastandovariancarcinomacelllineswithdifferingdoxorubicinresistance
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High-definition DNA methylation profiles from breast and ovarian carcinoma cell lines with differing doxorubicin resistance.

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