H3K27me3 ChIP-Seq analysis of ErbB2-driven mouse mammary tumour cells treated with GSK-126
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA561591 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10027153.fastq.gz | Fastqsanger.gz | |||
| SRR10027154.fastq.gz | Fastqsanger.gz | |||
| SRR10027155.fastq.gz | Fastqsanger.gz | |||
| SRR10027156.fastq.gz | Fastqsanger.gz | |||
| SRR10027157.fastq.gz | Fastqsanger.gz |
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Project description:Microarray analysis of ErbB2-driven mouse mammary tumour cells treated with GSK-126
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Project description:Monoclonal antibodies (mAbs) targeting the oncogenic receptor tyrosine kinase ERBB2/HER2, such as Trastuzumab, are the standard of care therapy for breast cancers driven by ERBB2 overexpression and activation. However, a substantial proportion of patients exhibits de novo resistance. Here, by comparing matched Trastuzumab-naïve and post-treatment patient samples from a neoadjuvant trial, we link resistance with elevation of H3K27me3, a repressive histone modification catalyzed by Polycomb Repressor Complex 2 (PRC2). In ErbB2+ breast cancer models, PRC2 silences endogenous retroviruses (ERVs) to suppress anti-tumor Type-I interferon (IFN) responses. In patients, elevated H3K27me3 in tumor cells following Trastuzumab treatment correlates with suppression of IFN-driven viral defense gene expression signatures and poor response. Using an immunocompetent model, we provide evidence that EZH2 inhibitors promote IFN-driven immune responses that enhance the efficacy of anti-ErbB2 mAbs, suggesting the potential clinical benefit of epigenomic reprogramming by H3K27me3 depletion in Trastuzumab-resistant disease.
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