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 language | English |
|---|---|
| Pages (from-to) | 1325-1336 |
| Number of pages | 12 |
| Journal | American Journal of Pathology |
| Volume | 170 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
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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 journal › Article
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TY - JOUR
T1 - A reduction of cyclooxygenase 2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice
AU - Yang, Wan Lin
AU - Cai, Kathy Qi
AU - Smedberg, Jennifer L.
AU - Smith, Elizabeth R.
AU - Klein-Szanto, Andres
AU - Hamilton, Thomas C.
AU - Xu, Xiangxi
PY - 2007/4/1
Y1 - 2007/4/1
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=34247874637&partnerID=8YFLogxK
U2 - 10.2353/ajpath.2007.060769
DO - 10.2353/ajpath.2007.060769
M3 - Article
VL - 170
SP - 1325
EP - 1336
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
ER -