COX-1 Suppression and Follicle Depletion in the Etiology of Menopause-Associated Ovarian Cancer
Final rept. 1 Apr 2007-30 Sep 2009
FOX CHASE CANCER CENTER PHILADELPHIA PA
Pagination or Media Count:
Menopause is defined as a permanent cessation of menstruation resulting from depletion of germs cells and loss of ovarian follicular activity. Menopausal ovaries undergo morphological changes that are likely related to the increased risk of ovarian cancer in the peri- and post-menopausal periods. The germ cell-deficient Wv mice recapitulate these post-menopausal alterations in ovarian morphology and develop tubular adenomas. Genetic deletion of cyclooxygenase 1 Cox-1 in the WvWv background reduced the tumor lesions nearly 3-fold in 4 month mice. Moreover, Cox-1 deletion appeared to delay maturation of small preantral follicles, thus delay follicle depletion and subsequently delay the tumor development. Pharmacological inhibitors of Cox- 1 also rescued the tumor phenotype and preserved primary follicles in aged mice. These findings suggest that Cox-1 activity may contribute to preneoplastic morphological changes of the ovarian surface epithelium, which can potentially be prevented by pharmacological inhibitors of Cox-1. Moreover, the observations indicate that depletion of follicles may underlie the etiological factors that influence ovarian cancer risk.
- Medicine and Medical Research