Rapid in vivo validation of candidate drivers derived from the PTEN-mutant prostate metastasis genome

Cho, Hyejin, Herzka, Tali, Stahlhut, Carlos, Watrud, Kaitlin, Robinson, Brian D., Trotman, Lloyd C. (May 2015) Rapid in vivo validation of candidate drivers derived from the PTEN-mutant prostate metastasis genome. Methods, 77-78. pp. 197-204. ISSN 1046-2023

URL: http://www.ncbi.nlm.nih.gov/pubmed/25592467
DOI: 10.1016/j.ymeth.2014.12.022

Abstract

Human genome analyses have revealed that increasing gene copy number alteration is a driving force of incurable prostate cancer (PC). Since most of the affected genes are hidden within large amplifications or deletions, there is a need for fast and faithful validation of drivers. However, classic genetic PC engineering in mouse makes this a daunting task because generation, breeding based combination of alterations and non-invasive monitoring of disease are too time consuming and costly. To address the unmet need, we recently developed RapidCaP mice, which endogenously recreate human PTEN-mutant metastatic PC based on Cre/Luciferase expressing viral infection, that is guided to PtenloxP/Trp53loxP prostate. Here we use a sensitized, non-metastatic Pten/ Trp53-mutant RapidCaP system for functional validation of human metastasis drivers in a much accelerated time frame of only 3-4 months. We used in vivo RNAi to target three candidate tumor suppressor genes FOXP1, RYBP and SHQ1, which reside in a frequent deletion on chromosome 3p and show that Shq1 cooperates with Pten and p53 to suppress metastasis. Our results thus demonstrate that the RapidCaP system forms a much needed platform for in vivo screening and validation of genes that drive endogenous lethal PC.

Item Type: Paper
Uncontrolled Keywords: Cancer gene discovery Tumor suppressors Mouse models RapidCaP Prostate cancer PTEN
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > PTEN
diseases & disorders > cancer > metastasis
diseases & disorders > cancer > cancer types > prostate cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL labs > Trotman lab
Depositing User: Matt Covey
Date: May 2015
Date Deposited: 16 Jan 2015 21:28
Last Modified: 30 Oct 2015 15:08
PMCID: PMC4429512
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31125

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