Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging

Courtney Yong; Devon L Moose; Nadine Bannick; Wade R Gutierrez; Marion Vanneste; Robert Svensson; Patrick Breheny; James A Brown; Rebecca D Dodd; Michael B Cohen; Michael D Henry

doi:10.1371/journal.pone.0232807

Back

Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging

Journal article

Open access

Peer reviewed

Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging

Courtney Yong, Devon L Moose, Nadine Bannick, Wade R Gutierrez, Marion Vanneste, Robert Svensson, Patrick Breheny, James A Brown, Rebecca D Dodd, Michael B Cohen, …

PloS one, Vol.15(9), pp.e0232807-e0232807

2020

DOI: 10.1371/journal.pone.0232807

PMCID: PMC7521703

PMID: 32986721

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0232807View

Published (Version of record) Open Access

Abstract

Here we have improved an existing mouse model of prostate cancer based on prostate-specific deletion of Pten and Trp53 by incorporating a Cre-activatable luciferase reporter. By coupling the deletion of those genes to the activation of a luciferase reporter, we were able to monitor tumor burden non-invasively over time. We show that, consistent with previous reports, deletion of both Pten and Trp53 on a C57BL/6 background accelerates tumor growth and results in both the loss of androgen receptor expression and castrate resistant tumors as compared with loss of Pten alone. Loss of Trp53 results in the development of sarcomatoid histology and the expression of markers of epithelial-to-mesenchymal transition Zeb1 and vimentin, with kinetics and penetrance dependent on whether one or both alleles of Trp53 were deleted. Homozygous deletion of Trp53 and Pten resulted in uniformly lethal disease by 25 weeks. While we were able to detect locally invasive disease in the peritoneal cavity in aggressive tumors from the double knockout mice, we were unable to detect lymphatic or hematogenous metastatic disease in lymph nodes or at distant sites.

Animals

Biomarkers, Tumor - genetics

Carcinogenesis

Disease Models, Animal

Epithelial-Mesenchymal Transition

Luminescent Measurements

Male

Mice

Mice, Inbred C57BL

Mice, Knockout

Monitoring, Physiologic

Prostatic Neoplasms, Castration-Resistant - genetics

PTEN Phosphohydrolase - genetics

Sequence Deletion

Tumor Suppressor Protein p53 - genetics

Details

Title: Subtitle: Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging
Creators: Courtney Yong - Roy J. and Lucille A. Carver College of Medicine
Devon L Moose - University of Iowa
Nadine Bannick - Roy J. and Lucille A. Carver College of Medicine
Wade R Gutierrez - Roy J. and Lucille A. Carver College of Medicine
Marion Vanneste - University of Iowa
Robert Svensson - University of Iowa
Patrick Breheny - University of Iowa
James A Brown - University of Iowa
Rebecca D Dodd - University of Iowa
Michael B Cohen - Wake Forest University
Michael D Henry - University of Iowa
Resource Type: Journal article
Publication Details: PloS one, Vol.15(9), pp.e0232807-e0232807
DOI: 10.1371/journal.pone.0232807
PMID: 32986721
PMCID: PMC7521703
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: R21 CA137490 / NCI NIH HHS T32 GM067795 / NIGMS NIH HHS T32 GM007337 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Biostatistics; Radiation Oncology; Urology; Internal Medicine
Record Identifier: 9984230629102771

Metrics

6 Record Views

6 Times Cited - Web of Science