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Description
Summary from GEO:

"To study genetic factors that influence the progression and therapeutic response of advanced prostate cancer, we developed a fast and flexible system that introduces genetic alterations relevant to human disease directly into the prostate glands of mice using tissue electroporation. These electroporation based genetically engineered mouse models (EPO-GEMM) recapitulate features of traditional germline models and, by modeling genetic factors linked to late stage human disease, can produce tumors that are metastatic and castration resistant. Unexpectedly, a subset of particularly metastatic tumors acquired WNT pathway alterations, which are also associated with metastatic prostate cancer in humans. Harnessing features linked to the EPO-GEMM approach, we validate the WNT pathway as a key event in driving metastatic disease, a finding that we confirm in an orthogonal approach using mouse prostate organoids. Moreover, we show that tumors harboring WNT pathway alterations are sensitive to pharmacological WNT pathway inhibition. Thus, by leveraging the power of EPO-GEMMs, our studies reveal a functional role for WNT signaling in driving prostate cancer metastasis and validate the WNT pathway as an actionable therapeutic target in metastatic prostate cancer."

Overall design from GEO:

"For RNA-seq analysis of the transcriptional profiles of MPten and MP EPO-GEMM prostate tumors, as well as normal anterior lobes of prostates of wild-type (WT) C57BL/6, total RNA was extracted from bulk tissue using the RNeasy Mini Kit (Qiagen). Purified polyA mRNA was subsequently fragmented, and first and second strand cDNA synthesis performed using standard Illumina mRNA TruSeq library preparation protocols. Double stranded cDNA was subsequently processed for TruSeq dual-index Illumina library generation."
Subject of Study
Mus musculus
Subject(s)
Prostatic Neoplasms
RNA-Seq
Tissue Engineering
Wnt Signaling Pathway
Access via GEO


Accession #: GSE139340

Access via BioProject


Accession #: PRJNA579352

Access via SRA


Accession #: SRP226854

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, BioProject, and SRA databases provides open access to these files.
Associated Publications
Leibold J, Ruscetti M, Cao Z, Ho Y, Baslan T, Zou M, Abida W, Feucht J, Han T, Barriga F, Tsanov K, Zamechek L, Kulick A, Amor C, Tian S, Rybczyk K, Salgado N, Sánchez-Rivera F, Watson P, de Stanchina E, Wilkinson J, Dow L, Abate-Shen C, Sawyers C, Lowe S. Somatic tissue engineering in mouse models reveals an actionable role for WNT pathway alterations in prostate cancer metastasis. Cancer Discovery. 2020; 10(7):1038-1057.
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

RNeasy Mini Kit

For purification of total RNA from cells, tissues, and yeast

Dataset Format(s)
CSV
Dataset Size
4.8 MB
Data Catalog Record Updated
2023-10-05