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
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: | https://repository.cshl.edu/id/eprint/31125 |
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