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(American Journal of Pathology. 2007;170:1325-1336.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060769

A Reduction of Cyclooxygenase 2 Gene Dosage Counters the Ovarian Morphological Aging and Tumor Phenotype in Wv Mice

Wan-Lin Yang, Kathy Qi Cai, Jennifer L. Smedberg, Elizabeth R. Smith, Andres Klein-Szanto, Thomas C. Hamilton and Xiang-Xi Xu

From the Department of Medical Oncology, Ovarian Cancer and Tumor Biology Programs, Fox Chase Cancer Center, Philadelphia, Pennsylvania

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 E2 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.






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Copyright © 2007 by the American Society for Investigative Pathology.