Project description:Recurrent point mutations in SPOP define a distinct molecular subclass of prostate cancer. Here, we describe the first mouse model showing that mutant SPOP drives prostate tumorigenesis in vivo. Conditional expression of mutant SPOP in the prostate dramatically altered phenotypes in the setting of Pten loss, with early neoplastic lesions (high-grade prostatic intraepithelial neoplasia) with striking nuclear atypia, and invasive poorly differentiated carcinoma. In mouse prostate organoids, mutant SPOP drove increased proliferation and a transcriptional signature consistent with human prostate cancer. Using these models and human prostate cancer samples, we show that SPOP mutation activates both PI3K/mTOR and androgen receptor (AR) signaling, effectively uncoupling the normal negative feedback between these two pathways. Associated RNA-seq data deposited in GEO: GSE94839.
Project description:Gene expression data from the RNA sequencing of laser microdissected pancreatic intraepithelial neoplasia and pancreatic normal ducts.
Project description:High grade prostate intraepithelial neoplasia (HGPIN) is a precursor lesion for prostate cancer. The APT121 mouse is a model of early stage prostate cancer that develops PIN lesions that progress to adenocarcinoma over a period of 6 months. At 12 wks of age APT121 mouse prostate contains mostly high grade PIN lesions. We compared the transcript profile of RNA from the anterior prostate of age- and genetic background matched wild type and APT121 mice using Affymetric microarrays.
