A reduction of cyclooxygenase 2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice.

Abstract	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.
Authors	Wan-Lin Yang, Kathy Qi Cai, Jennifer L Smedberg, Elizabeth R Smith, Andres Klein-Szanto, Thomas C Hamilton, Xiang-Xi Xu
Journal	The American journal of pathology (Am J Pathol) Vol. 170 Issue 4 Pg. 1325-36 (Apr 2007) ISSN: 0002-9440 [Print] United States
PMID	17392171 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	Cyclooxygenase Inhibitors Pyrazoles Sulfonamides Ptgs2 protein, mouse Cyclooxygenase 2 Celecoxib Dinoprostone Indomethacin
Topics	Adenoma (genetics, metabolism, pathology) Aging (pathology) Animals Blotting, Western Celecoxib Cell Transformation, Neoplastic (drug effects) Cyclooxygenase 2 (deficiency, genetics, metabolism) Cyclooxygenase Inhibitors (administration & dosage, pharmacology) Dinoprostone (metabolism) Epithelium (metabolism, pathology) Female Gene Dosage Heterozygote Homozygote Humans Inbreeding Indomethacin (administration & dosage, pharmacology) Male Mice Mice, Inbred C57BL Mice, Knockout Ovarian Neoplasms (genetics, metabolism, pathology) Ovary (drug effects, metabolism, pathology) Phenotype Pyrazoles (administration & dosage, pharmacology) Sulfonamides (administration & dosage, pharmacology)

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