title: Slow disease progression in a C57BL/6 pten-deficient mouse model of prostate cancer.
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 Pten(p-/-) 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 Pten(p-/-) 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 Pten(p-/-) 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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, 6-510 Bowen Science Bldg., University of Iowa, Iowa City, IA 52240, USA.
authors.forename: Robert U
authors.initials: RU
authors.lastname: Svensson
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Haverkamp
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Thedens
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cohen
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Ratliff
authors.forename: Michael D
authors.initials: MD
authors.lastname: Henry
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D019426:Integrases; D008156:Luciferases / Q000378:metabolism; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D010641:Phenotype; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology*; D013997:Time Factors
chemical_list: D008156:Luciferases; C045073:Cre recombinase; D019426:Integrases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse