Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice

Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the var...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006-05, Vol.66 (9), p.4701-4707
Main Authors: LYONS, Scott K, LIM, Ed, JENKINS, Darlene, CLERMONT, Anne O, DUSICH, Joan, LINGYUN ZHU, CAMPBELL, Kenneth D, COFFEE, Richard J, GRASS, David S, HUNTER, John, PURCHIO, Tony
Format: Article
Language:English
Subjects:
Androgens - deficiency
Androgens - metabolism
Animals
Antineoplastic agents
Biological and medical sciences
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Disease Models, Animal
Genes, Reporter - genetics
Humans
Image Processing, Computer-Assisted - methods
In Situ Hybridization
Luciferases, Firefly - analysis
Luciferases, Firefly - biosynthesis
Luciferases, Firefly - genetics
Luminescent Measurements - methods
Male
Medical sciences
Mice
Mice, Transgenic
Pharmacology. Drug treatments
Promoter Regions, Genetic
Prostate - metabolism
Prostate - physiology
Prostate-Specific Antigen - analysis
Prostate-Specific Antigen - biosynthesis
Prostate-Specific Antigen - genetics
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Simian virus 40
Tumors
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Summary:Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the variable onset and non-visible nature of prostate tumor development limit their use for such applications. We now report the generation of a transgenic reporter mouse that should obviate these limitations by enabling noninvasive in vivo bioluminescence imaging of normal and spontaneously transformed prostate tissue in the mouse. We used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to achieve specific and robust expression of firefly luciferase in the prostate glands of transgenic mice. Ex vivo bioluminescence imaging and in situ hybridization analysis confirmed that luciferase expression was restricted to the epithelium in all four lobes of the prostate. We also show that PSA-Luc mice exhibit decreased but readily detectable levels of in vivo bioluminescence over extended time periods following androgen ablation. These results suggest that this reporter should enable in vivo imaging of both androgen-dependent and androgen-independent prostate tumor models. As proof-of-principle, we show that we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can be successfully used to image tumor response to androgen ablation in transgenic mice and, as a result, that we can rapidly identify individual animals capable of sustaining tumor growth in the absence of androgen.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-05-3598