github link
Accession IconGSE59427

Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis

Organism Icon Mus musculus
Sample Icon 18 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

Submitter Supplied Information

Description
Alterations of chromatin modifiers are frequent in cancer but their functional consequences remain often unclear. Focusing on the Polycomb protein EZH2 that deposits H3K27me3 mark, we showed that its high expression in solid tumors is a consequence, and not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process is malfunctioning in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes are actually of poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes consequent to EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.
PubMed ID
Total Samples
30
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Specimen part
Processing Information
Additional Metadata
No rows found
Loading...