Cyclooxygenase-two (COX-2) modulates proliferation in aggressive fibromatosis (desmoid tumor).
Oncogene
; 20(4): 451-60, 2001 Jan 25.
Article
em En
| MEDLINE
| ID: mdl-11313976
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transativadores
/
Prostaglandina-Endoperóxido Sintases
/
Fibromatose Agressiva
/
Isoenzimas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article