Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model
Article first published online: 6 MAR 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 67, Issue 7, pages 685–691, 15 May 2007
How to Cite
Hsieh, C.-L., Xie, Z., Yu, J., Martin, W. D., Datta, M. W., Wu, G.-J. and Chung, L. W.K. (2007), Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model. Prostate, 67: 685–691. doi: 10.1002/pros.20510
- Issue published online: 28 MAR 2007
- Article first published online: 6 MAR 2007
- Manuscript Accepted: 28 JUL 2006
- Manuscript Received: 1 JUN 2006
- NIH. Grant Numbers: 1PO1CA098912-01, 1U54CA119338, 5P20GM072069
- DoD. Grant Numbers: DAMD 17-03-2-0033, W81XWH-05-1-0024
- supra prostate specific antigen (sPSA) promoter;
- prostate cancer bone metastasis;
- bigenic transgenic mouse;
- TRAMP model;
- bioluminescence imaging
We previously established a bioluminescent transgenic mouse model, sPSA-Luc, with luciferase gene expression restricted to the prostate under the control of the supra prostate-specific antigen (sPSA) promoter. We now assess the feasibility of generating bigenic mice, TRAMP-Luc, with the sPSA-Luc as the founder strain crossbred with TRAMP (transgenic adenocarcinoma mouse prostate) mice, to evaluate non-invasively the metastatic potential of prostate tumors.
TRAMP-Luc mice were obtained as [C57BL/6 TRAMP × FVB sPSA-Luc] F1 offspring. Tumor development in 10 TRAMP-Luc males was followed by bioluminescence imaging from 8 to 24 weeks of age. Immunohistochemical (IHC) staining for T antigen (Tg), androgen receptor (AR), luciferase and/or pathological analysis verified the tumor distribution in the imaged tissues including prostate gland, lymph node and bone.
Group I animals that presented with no grossly visible tumors showed prostate-confined bioluminescence with slightly increased signal intensity with age. Group II animals that developed large tumors displayed a widely distributed and biphasic bioluminescence pattern. The peak was reached between 10 and 14 weeks of age, then markedly decreased or even disappeared beyond week 16, except for one mouse that showed an increased bioluminescence signal at the jaw bone and hind limbs at week 22. These tumors were shown by IHC to contain Tg but lost AR and luciferase beyond week 16 in poorly differentiated prostate tumors.
A direct correlation between bioluminescence emission and AR expression was found in TRAMP-Luc tumor progression model. This model allows non-invasive imaging of prostate cancer metastases to bone and soft tissues. Prostate 67: 685–691, 2007. © 2007 Wiley-Liss, Inc.