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, Xiangxi Xu

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1325-1336
Number of pages12
JournalAmerican Journal of Pathology
Volume170
Issue number4
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

Fingerprint

Gene Dosage
Cyclooxygenase 2
Postmenopause
Phenotype
Cyclooxygenase 1
Cyclooxygenase Inhibitors
Prostaglandin-Endoperoxide Synthases
Dinoprostone
Germ Cells
Adenoma
Ovarian Neoplasms
Ovary
Neoplasms
Epithelium
Pharmacology
Incidence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

A reduction of cyclooxygenase 2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice. / Yang, Wan Lin; Cai, Kathy Qi; Smedberg, Jennifer L.; Smith, Elizabeth R.; Klein-Szanto, Andres; Hamilton, Thomas C.; Xu, Xiangxi.

In: American Journal of Pathology, Vol. 170, No. 4, 01.04.2007, p. 1325-1336.

Research output: Contribution to journalArticle

Yang, Wan Lin ; Cai, Kathy Qi ; Smedberg, Jennifer L. ; Smith, Elizabeth R. ; Klein-Szanto, Andres ; Hamilton, Thomas C. ; Xu, Xiangxi. / A reduction of cyclooxygenase 2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice. In: American Journal of Pathology. 2007 ; Vol. 170, No. 4. pp. 1325-1336.
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