First Author | Yang WL | Year | 2007 |
Journal | Am J Pathol | Volume | 170 |
Issue | 4 | Pages | 1325-36 |
PubMed ID | 17392171 | Mgi Jnum | J:120134 |
Mgi Id | MGI:3703938 | Doi | 10.2353/ajpath.2007.060769 |
Citation | Yang WL, et al. (2007) A reduction of cyclooxygenase 2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice. Am J Pathol 170(4):1325-36 |
abstractText | Menopausal ovaries undergo morphological changes, known as ovarian aging, which are implicated in the high incidence of ovarian cancer occurring during the perimenopausal and immediate postmenopausal periods. The germ cell-deficient Wv mice recapitulate these postmenopausal alterations in ovarian morphology and develop tubular adenomas. We demonstrate that a reduction of cyclooxygenase 2 gene dosage rescued the ovarian aging phenotype of the Wv mice, whereas homozygous deletion was accompanied by a compensatory increase in ovarian cyclooxygenase 1 expression and prostaglandin E(2) synthesis. Cyclooxygenase inhibitors also reduced the tumor phenotype in a preliminary study. These findings suggest that increased cyclooxygenase activity contributes to the preneoplastic morphological changes of the ovarian surface epithelium, which can be reversed by a reduction of gene dosage achieved by either genetic or pharmacological approaches. |