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Series GSE39783 Query DataSets for GSE39783
Status Public on May 01, 2014
Title Estrogen deprivation alters epigenetic modifications in breast cancer cells - HOXC10 loss in endocrine resistance
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Postmenopausal breast cancer patients benefit from aromatase inhibitors (AIs) that reduce the levels of estrogens critical for the growth of estrogen receptor (ER)-positive tumors. Unfortunately, many tumors are resistant to AI, and we are only beginning to understand the complex mechanisms underlying treatment resistance. Here we set out to determine whether epigenetic changes could contribute to therapy resistance. For AI-resistance models, we used previously established MCF-7 cell clones, termed C4-12 and long-term estrogen deprivation (LTED), that were isolated after being cultured in estrogen-free media for 9 months and 18–24 months, respectively. Methyl CpG Binding Domain (MBD) - pull down followed by affymetrix promoter array was used to detect promoter methylation patterns in these cell lines. These studies identified widespread genomic hyper- and hypomethylation events, with a significant enrichment of promoter hypermethylation of development-associated genes in both cell lines. A developmentally regulated gene that was heavily methylated and lost expression in both cell-line systems was HOXC10. Moreover, we found that HOXC10 is an estrogen-regulated gene and lack of ER regulation is associated with progressive epigenetic silencing through EZH2/H3K27me3 and DNA hypermethylation. Stable knockdown of HOXC10 in MCF-7 cells resulted in increased cell growth, reduced cell apoptosis, and increased cell motility. A preliminary study using AI-treated breast tumors did not show significant associations, however, the numbers were small. We identified HOXC10 methylation as a novel determinant of endocrine resistance. Also, we revealed that epigenetic reprogramming of genes involved in development may be a fundamental phenomenon in hormone resistance. Therefore, our study might provide the basis for the expansion of clinical markers for endocrine resistance and future clinical trials such as combination of endocrine and epigenetic therapies.
Overall design Long-term estrogen deprived previously established MCF-7 cell clones termed C4-12 and LTED genomic DNA subjected to Methyl CpG Binding Domain (MBD) - pull down followed by affymetrix promoter array to detect promoter methylation patterns
Contributor(s) Yuanxin X, Thushangi P
Citation(s) 24670685
Submission date Jul 31, 2012
Last update date Jan 21, 2015
Contact name Yuanxin Xi
Phone 530-220-2067
Organization name The University of Texas MD Anderson Cancer Center
Department Bioinformatics and Computational Biology
Street address 1400 Pressler St
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL5082 [Hs_PromPR] Affymetrix Human Promoter 1.0R Array
Samples (2)
GSM978997 C412
GSM978998 LTED
BioProject PRJNA171707

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE39783_MCF7_0hr_1.CEL.gz 28.1 Mb (ftp)(http) CEL
GSE39783_MCF7_0hr_2.CEL.gz 27.6 Mb (ftp)(http) CEL
GSE39783_MCF7_0hr_3.CEL.gz 27.8 Mb (ftp)(http) CEL
GSE39783_MCF7_0hr_4.CEL.gz 28.3 Mb (ftp)(http) CEL
GSE39783_RAW.tar 222.7 Mb (http)(custom) TAR (of BAR, CEL)
Processed data provided as supplementary file

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