|
| Status |
Public on Aug 01, 2020 |
| Title |
Epigenetic and Expression Profiling of Tissue Selective Estrogen Compounds in Breast Epithelial Cell Lines (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Current approaches to menopausal hormone therapy consist of compounds which provide tissue specific beneficial effects while working to minimize any increase in cancer risk associated with replacement therapy. In this study, an examination of the genomic distribution of histone modification and expression changes in two breast epithelial cell lines, the normal MCF10A cell line and the MCF-7 breast cancer cell line, upon treatment with several of the current therapies used for treating post-menopausal symptoms is presented. Analysis of the observed changes upon treatment with either 17-estradiol (E2), a combined treatment with the top 10 most abundant Premarin chemical equivalents (EC10), the non-steroidal SERM, Bazadoxifene (BZA) and the TSEC; BZA combined with EC10 (Duavee) or BZA combined with E2 provides evidence of expression changes in genes involved in DNA replication, nucleosome assembly, RNA-splicing and processing, biological regulation and cell signaling, and many of the known steroid response genes. There were distinct global changes in chromatin states observed that were specific to each of the breast epithelial cell type normal, basal MCF10A and ESR/PGR positive luminal breast cancer MCF7 cell lines and selective changes observed upon treatment with each of the treatment groups. Specifically, we observed a global loss of H3K4ac upon treatment with BZA. These changes were observed in both ESR1 bound and non-bound regions suggesting modifications in both promoters and enhancer regions. The levels of H3K4ac upon treatment of BZA showed a decrease below basal non-treated H3K4ac levels in MCF7. There was an increase observed with E2 and EC10 treatment in MCF7 that was mitigated by the addition of BZA to either steroid as a combined treatment. This study provides a better understanding of the role of epigenetic modifications in endocrine responsiveness and provides evidence of an improved therapeutic profile for combined TSEC compounds for treating and managing the overall physiological effects of declining estrogen.
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| |
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| Overall design |
6 drug treatments in 2 cell lines with 3 biological replicates
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| |
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| Contributor(s) |
Messier TL, Boyd JR, Stein GS |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Aug 09, 2017 |
| Last update date |
Aug 01, 2020 |
| Contact name |
Jonathan AR Gordon |
| E-mail(s) |
Jonathan.A.Gordon@uvm.edu
|
| Organization name |
University of Vermont
|
| Department |
Biochemistry
|
| Street address |
89 Beaumont Ave Given E209
|
| City |
Burlington |
| State/province |
VT |
| ZIP/Postal code |
05405 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
|
| Samples (36)
|
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| This SubSeries is part of SuperSeries: |
| GSE102472 |
Epigenetic and Expression Profiling of Tissue Selective Estrogen Compounds in Breast Epithelial Cell Lines |
|
| Relations |
| BioProject |
PRJNA397794 |
| SRA |
SRP115154 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102469_MCF10A_bza_merged_norm_neg.bw |
97.4 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_bza_merged_norm_pos.bw |
98.4 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_ctrl_merged_norm_neg.bw |
306.8 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_ctrl_merged_norm_pos.bw |
305.2 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_e2_merged_norm_neg.bw |
388.9 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_e2_merged_norm_pos.bw |
385.5 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_e2bza_merged_norm_neg.bw |
224.3 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_e2bza_merged_norm_pos.bw |
226.8 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_gc10_merged_norm_neg.bw |
248.1 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_gc10_merged_norm_pos.bw |
247.1 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_gc10bza_merged_norm_neg.bw |
309.8 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF10A_gc10bza_merged_norm_pos.bw |
307.8 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_bza_merged_norm_neg.bw |
147.1 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_bza_merged_norm_pos.bw |
144.6 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_ctrl_merged_norm_neg.bw |
185.4 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_ctrl_merged_norm_pos.bw |
184.7 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_e2_merged_norm_neg.bw |
130.1 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_e2_merged_norm_pos.bw |
130.1 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_e2bza_merged_norm_neg.bw |
45.8 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_e2bza_merged_norm_pos.bw |
44.9 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_gc10_merged_norm_neg.bw |
162.9 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF7_gc10_merged_norm_pos.bw |
160.1 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF_gc10bza_merged_norm_neg.bw |
104.3 Mb |
(ftp)(http) |
BW |
| GSE102469_MCF_gc10bza_merged_norm_pos.bw |
101.6 Mb |
(ftp)(http) |
BW |
| GSE102469_drug_treatments_RNAseq_ENSG_counts.txt.gz |
4.9 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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