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ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer

UID: 10858

Publisher(s): Dryad

Description
Summary from Dryad:

"Abstract:
The mechanisms underlying ETS-driven prostate cancer initiation and progression remain poorly understood due to a lack of model systems that recapitulate this phenotype. We generated a genetically engineered mouse with prostate-specific expression of the ETS factor, ETV4, at lower and higher protein dosages through mutation of its degron. Lower-level expression of ETV4 caused mild luminal cell expansion without histologic abnormalities and higher-level expression of stabilized ETV4 caused prostatic intraepithelial neoplasia (mPIN) with 100% penetrance within 1 week. Tumor progression was limited by p53-mediated senescence and Trp53 deletion cooperated with stabilized ETV4. The neoplastic cells expressed differentiation markers such as Nkx3.1 recapitulating luminal gene expression features of untreated human prostate cancer. Single-cell and bulk RNA-sequencing showed stabilized ETV4 induced a novel luminal-derived expression cluster with signatures of the cell cycle, senescence, and epithelial to mesenchymal transition. These data suggest that ETS overexpression alone, at sufficient dosage, can initiate prostate neoplasia."

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Subject of Study
Subject(s)
Access Restrictions
Free to All
Access Instructions
Download from Dryad to access
DOI
10.5061/dryad.v41ns1s0s
Associated Publications
Equipment Used
Illumina HiSeq 2500
Software Used
ENCODE ATAC-seq pipeline
STAR Aligner
UMAP
Dataset Format(s)
Microsoft Excel
Dataset Size
2,265 KB (compressed)
Data Catalog Record Updated
2023-09-27