High-density array analysis of DNA methylation in tamoxifen-resistant breast cancer cell lines.

TitleHigh-density array analysis of DNA methylation in tamoxifen-resistant breast cancer cell lines.
Publication TypeJournal Article
Year of Publication2014
AuthorsWilliams KE, Anderton DL, Lee MP, Pentecost BT, Arcaro KF
JournalEpigenetics
Volume9
Issue2
Date Published2014 Feb
ISSN1559-2308
Abstract

Roughly two-thirds of all breast cancers are ERα-positive and can be treated with the antiestrogen, Tamoxifen, however resistance occurs in 33% of women who take the drug for more than 5 y. Aberrant DNA methylation, an epigenetic mechanism that alters gene expression in cancer, is thought to play a role in this resistance. To develop an understanding of Tamoxifen-resistance and identify novel pathways and targets of aberrant methylation, DNA from MCF-7 breast cancer cells and Tamoxifen-resistant derivatives, TMX2-11 and TMX2-28, were analyzed using the Illumina HumanMethylation450 BeadChip. Normalizing against MCF-7 values, ERα-positive TMX2-11 had 4,000 hypermethylated sites and ERα-negative TMX2-28 had over 33,000. Analysis of CpG sites altered in both TMX2-11 and TMX2-28 revealed that the Tamoxifen-resistant cell lines share 3000 hypermethylated and 200 hypomethylated CpGs. ZNF350 and MAGED1, two genes hypermethylated in both cell lines, were examined in greater detail. Treatment with 5-aza-2’deoxycitidine caused a significant reduction in promoter methylation of both ZNF350 and MAGED1 and a corresponding increase in expression in TMX2-28. A similar relationship between methylation and expression was not detected in TMX2-11. Our findings are indicative of the variable responses to methylation-targeted breast cancer therapy and highlight the need for biomarkers that accurately predict treatment outcome.

Alternate JournalEpigenetics
PubMed ID24225485