Reference SummaryKlein RD, Cancer Res 2005 Mar 1;65(5):1808-13
Title |
Transitional cell hyperplasia and carcinomas in urinary bladders of transgenic mice with keratin 5 promoter-driven cyclooxygenase-2 overexpression. |
Authors |
Klein RD; Van Pelt CS; Sabichi AL; Dela Cerda J; Fischer SM; Furstenberger G; Muller-Decker K |
Journal |
Cancer Res |
Volume |
65 |
Issue |
5 |
Year |
2005 |
Pages |
1808-13 |
Abstract |
The inducible form of cyclooxygenase (COX), COX-2, is up-regulated in many epithelial cancers and its prostaglandin products increase proliferation, enhance angiogenesis, and inhibit apoptosis in several tissues. Pharmacologic inhibition and genetic deletion studies showed a marked reduction of tumor development in colon and skin. COX-2 has also been strongly implicated in urinary bladder cancer primarily by studies with nonselective COX- and COX-2-selective inhibitors. We now show that forced expression of COX-2, under the control of a keratin 5 promoter, is sufficient to cause transitional cell hyperplasia (TCH) in 17% and 75% of the heterozygous and homozygous transgenic lines, respectively, in an age-dependent manner. TCH was strongly associated with inflammation, primarily nodules of B lymphocytes; some T cells and macrophage infiltration were also observed. Additionally, transitional cell carcinoma was observed in approximately 10% of the K5.COX-2 transgenic mice; no TCH or transitional cell carcinoma was observed in wild-type bladders. Immunohistochemistry for vascular proliferation and vascular endothelial growth factor showed significant increases above that in wild-type urinary bladders. Our results suggest that overexpression of COX-2 is sufficient to cause hyperplasia and carcinomas in the urinary bladder. Therefore, inhibition of COX-2 should continue to be pursued as a potential chemopreventive and therapeutic strategy. |
Links |
J:96997 – MGI References 15753378 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| NMRI-Tg(K5-Ptgs2)667Kmd | Urinary bladder transitional cell carcinoma | Urinary bladder |
8.33 |
||
| NMRI-Tg(K5-Ptgs2)675Kmd | Urinary bladder transitional cell carcinoma | Urinary bladder |
10 |
||
| NMRI | Urinary bladder transitional cell carcinoma | Urinary bladder |
0 |
||
| NMRI-Tg(K5-Ptgs2)667Kmd | Urinary bladder transitional cell hyperplasia | Urinary bladder |
16.67 |
||
| NMRI-Tg(K5-Ptgs2)675Kmd | Urinary bladder transitional cell hyperplasia | Urinary bladder |
75 |
||
| NMRI | Urinary bladder transitional cell hyperplasia | Urinary bladder |
0 |