PLX261175

GSE78285: Modeling the ESR1 tyrosine 537 mutation with CRISPR-Cas9 for mechanistic studies and evaluation of therapeutic approaches for metastatic breast cancer [RNA-Seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Estrogen receptor- (ER) 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 ER target genes is elevated in the absence of estrogen. ER ChIP-seq was carried out to map global ER 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. SOURCE: Van,Thuy Mai,Nguyen (v.nguyen12@imperial.ac.uk) - Simak Ali's lab Imperial College London