title: Noninvasive bioluminescence imaging of normal and spontaneously transformed prostate tissue in mice.
abstract: 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.
authors.affiliation: Xenogen Corp., Alameda, California 94501, USA. scott.lyons@xenogen.com
authors.forename: Scott K
authors.initials: SK
authors.lastname: Lyons
authors.forename: Ed
authors.initials: E
authors.lastname: Lim
authors.forename: Anne O
authors.initials: AO
authors.lastname: Clermont
authors.forename: Joan
authors.initials: J
authors.lastname: Dusich
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhu
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Campbell
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Coffee
authors.forename: David S
authors.initials: DS
authors.lastname: Grass
authors.forename: John
authors.initials: J
authors.lastname: Hunter
authors.forename: Tony
authors.initials: T
authors.lastname: Purchio
authors.forename: Darlene
authors.initials: D
authors.lastname: Jenkins
mesh_terms: D000728:Androgens / Q000172:deficiency / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D017403:In Situ Hybridization; D049409:Luciferases, Firefly / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism / Q000502:physiology; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D000728:Androgens; D049409:Luciferases, Firefly; D017430:Prostate-Specific Antigen