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| Status |
Public on Oct 25, 2016 |
| Title |
Modeling the ESR1 tyrosine 537 mutation with CRISPR-Cas9 for mechanistic studies and evaluation of therapeutic approaches for metastatic breast cancer [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Estrogen receptor-α (ERα) is an important driver of breast cancer and is the target for hormonal therapies, anti-estrogens and drugs that limit estrogen biosynthesis (aromatase inhibitors). Mutations in the ESR1 gene identified in metastatic breast cancer provide a potential mechanism for acquired resistance to hormone therapies. We have used CRISPR-Cas9 mediated genome editing in the MCF-7 breast cancer cell line, generating MCF-7-Y537S. MCF-7-Y537S cells encode a wild-type (tyrosine 537) and a mutant (serine 537) allele. Growth of the line is estrogen-independent and expression of ERα target genes is elevated in the absence of estrogen. ER ChIP-seq was carried out to map global ERα binding sites in the presence and absence of estrogen. RNA-seq following estrogen treatment was used for gene expression analysis. We show that expression of ER target genes and ER recruitment to ER binding regions is similar in MCF-7 and MCF-7-Y537S cells, except that ER recruitment to DNA and expression of ER target genes is frequently elevated in the absence of estrogen.
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| Overall design |
Hormone depleted MCF7 Luc or Y537S cells were treated with 10nM E2 or ethanol, as vehicle control, for 8 hours, with 3 replicates (2 replicates for Y537S + E2). RNA-seq was carried out using Illumina Hiseq 2500.
|
| Web link |
http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016382a.html
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| |
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| Contributor(s) |
Ali S, Harrod A, Nguyen V |
| Citation(s) |
27748765 |
| |
| Submission date |
Feb 24, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Van Thuy Mai Nguyen |
| E-mail(s) |
[email protected]
|
| Organization name |
Institute of cancer research
|
| Department |
Cancer Biology
|
| Street address |
237 Fulham Rd, Chester Beatty Laboratories, third floor
|
| City |
London |
| ZIP/Postal code |
SW3 6JB |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (11)
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| This SubSeries is part of SuperSeries: |
| GSE78286 |
Modeling the ESR1 tyrosine 537 mutation with CRISPR-Cas9 for mechanistic studies and evaluation of therapeutic approaches for metastatic breast cancer |
|
| Relations |
| BioProject |
PRJNA313091 |
| SRA |
SRP070779 |
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