Journal article
Slow Disease Progression in a C57BL/6 Pten-Deficient Mouse Model of Prostate Cancer
The American journal of pathology, Vol.179(1), pp.502-512
07/2011
DOI: 10.1016/j.ajpath.2011.03.014
PMCID: PMC3123867
PMID: 21703427
Abstract
Prostate-specific deletion of Pten in mice has been reported to recapitulate histological progression of human prostate cancer. To improve on this model, we introduced the conditional ROSA26 luciferase reporter allele to monitor prostate cancer progression via bioluminescence imaging and extensively backcrossed mice onto the albino C57BL/6 genetic background to address variability in tumor kinetics and to enhance imaging sensitivity. Bioluminescence signal increased rapidly in Ptenp−/− mice from 3 to 11 weeks, but was much slower from 11 to 52 weeks. Changes in bioluminescence signal were correlated with epithelial proliferation. Magnetic resonance imaging revealed progressive increases in prostate volume, which were attributed to excessive fluid retention in the anterior prostate and to expansion of the stroma. Development of invasive prostate cancer in 52-week-old Ptenp−/− mice was rare, indicating that disease progression was slowed relative to that in previous reports. Tumors in these mice exhibited a spontaneous inflammatory phenotype and were rapidly infiltrated by myeloid-derived suppressor cells. Although Ptenp−/− tumors responded to androgen withdrawal, they failed to exhibit relapsed growth for up to 1 year. Taken together, these data identify a mild prostate cancer phenotype in C57BL/6 prostate-specific Pten-deficient mice, reflecting effects of the C57BL/6 genetic background on cancer progression. This model provides a platform for noninvasive assessment of how genetic and environmental risk factors may affect disease progression.
Details
- Title: Subtitle
- Slow Disease Progression in a C57BL/6 Pten-Deficient Mouse Model of Prostate Cancer
- Creators
- Robert U Svensson - University of IowaJessica M Haverkamp - Purdue University West LafayetteDaniel R Thedens - University of IowaMichael B Cohen - University of IowaTimothy L Ratliff - Purdue University West LafayetteMichael D Henry - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.179(1), pp.502-512
- DOI
- 10.1016/j.ajpath.2011.03.014
- PMID
- 21703427
- PMCID
- PMC3123867
- NLM abbreviation
- Am J Pathol
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Publisher
- American Society for Investigative Pathology
- Grant note
- name: University of Iowa Cancer and Aging Program, award: 5 P20 CA103672; name: NIH, award: R21-CA137490, RC1-ES018097, R21-CA154126
- Language
- English
- Date published
- 07/2011
- Academic Unit
- Radiology; Electrical and Computer Engineering; Molecular Physiology and Biophysics; Pathology; Radiation Oncology; Urology
- Record Identifier
- 9984197913202771
Metrics
14 Record Views