| First Author | Poon R | Year | 2001 |
| Journal | Oncogene | Volume | 20 |
| Issue | 4 | Pages | 451-60 |
| PubMed ID | 11313976 | Mgi Jnum | J:69222 |
| Mgi Id | MGI:1934310 | Doi | 10.1038/sj.onc.1204107 |
| Citation | Poon R, et al. (2001) Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor). Oncogene 20(4):451-60 |
| abstractText | Aggressive fibromatosis is a locally invasive soft tissue lesion. Seventy-five per cent of cases harbor a somatic mutation in either the APC or beta-catenin genes, resulting in beta-catenin protein stabilization. Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin synthesis that modulates the formation of colonic neoplasia, especially in cases due to mutations resulting in beta-catenin stabilization. Human aggressive fibromatoses and lesions from the Apc+/Apc1638N mouse (a murine model for Apc-driven fibromatosis) demonstrated elevated COX-2 levels. COX-2 blockade either by the selective agent DFU or by non-selective COX blocking agents results in reduced proliferation in human tumor cell cultures. Breeding mice with Cox-2-/- mice resulted in no difference in number of aggressive fibromatoses formed, but in a smaller tumor size, while there was a decrease in number of GI lesions by 50%. Mice fed various COX blocking agents also showed a decline in tumor size. COX-2 expression was regulated by tcf-dependent transcription in this lesion. COX-2 partially regulates proliferation due to beta-catenin stabilization in aggressive fibromatosis. Although COX blockade alone does not cause tumor regression, this data suggests that it may have a role as an adjuvant therapy to slow tumor growth in this lesion. |
