Non-invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model

Chia Ling Hsieh, Zhihui Xie, Jie Yu, W. David Martin, Milton W. Datta, Guang Jer Wu, Leland W K Chung

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

BACKGROUND. 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. METHODS. TRAMP-Luc mice were obtained as [C57BL/6 TRAMP x 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. RESULTS. 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. CONCLUSION. 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.

Original languageEnglish
Pages (from-to)685-691
Number of pages7
JournalProstate
Volume67
Issue number7
DOIs
Publication statusPublished - May 15 2007
Externally publishedYes

Keywords

  • Bigenic transgenic mouse
  • Bioluminescence imaging
  • Prostate cancer bone metastasis
  • Supra prostate specific antigen (sPSA) promoter
  • TRAMP model

ASJC Scopus subject areas

  • Urology

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