| First Author | Wang X | Year | 2008 |
| Journal | Carcinogenesis | Volume | 29 |
| Issue | 1 | Pages | 120-8 |
| PubMed ID | 17942462 | Mgi Jnum | J:131198 |
| Mgi Id | MGI:3773134 | Doi | 10.1093/carcin/bgm226 |
| Citation | Wang X, et al. (2008) The resistance to the tumor suppressive effects of COX inhibitors and COX-2 gene disruption in TRAMP mice is associated with the loss of COX expression in prostate tissue. Carcinogenesis 29(1):120-8 |
| abstractText | Over-expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) has been demonstrated to play a significant role in the tumorigenesis of colon, lung, breast, bladder and skin. However, inconsistent and controversial reports on the expression and activity of COX-2 in prostate cancer raised the question of whether COX-2 plays a pivotal role in prostate carcinogenesis. To address this question, we examined the effects of COX-2 inhibition on prostate tumorigenesis in the transgenic adenocarcinoma mouse prostate (TRAMP) model. Three-week-old TRAMP mice were fed control, celecoxib- or indomethacin-supplemented diets for 27 weeks. A TRAMP/COX-2 knockout mouse model was also generated to determine the effects of the loss of the COX-2 gene on prostate tumorigenesis in TRAMP mice. These studies demonstrated that neither non-steroidal anti-inflammatory drugs (NSAIDs) nor genetic disruption of COX-2 was inhibitory in terms of tumor and metastases incidence, lobe weight or types of pathological lesions. A careful analysis of wild-type and TRAMP tissues was undertaken for the expression of cyclooxygenase-1 (COX-1) and COX-2 using immunoblotting, quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemistry approaches in TRAMP dorsal prostate tissue from 10- and 16-week-old, as well as tumor from 30-week-old mice. We found that the expression of COX-1 and COX-2 dramatically decreased during TRAMP carcinogenesis. Using the probasin promoter, a COX-2 over-expressing mouse model was also generated but failed to show any pathology in any of the prostate lobes. Collectively, our results suggest that COX-2 may not play a tumorigenic role during prostate carcinogenesis in the TRAMP model. |
