title: Induction of a menopausal state alters the growth and histology of ovarian tumors in a mouse model of ovarian cancer.
abstract: OBJECTIVE
  Ovarian cancer is often diagnosed in women after menopause when the levels of the serum gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are increased because of the depletion of growing follicles within the ovary. The ability of FSH and LH to modulate the disease has not been well studied owing to a lack of physiologically relevant models of ovarian cancer. In this study, 4-vinylcyclohexene diepoxide (VCD) was used to deplete ovarian follicles and increase the levels of circulating FSH and LH in the tgCAG-LS-TAg mouse model of ovarian cancer.
  
  
  METHODS
  VCD-induced follicle depletion was performed either before or after induction of the oncogene SV40 large and small T-antigens in the ovarian surface epithelial cells of tgCAG-LS-TAg mice, which was mediated by the intrabursal delivery of an adenovirus expressing Cre recombinase (AdCre).
  
  
  RESULTS
  tgCAG-LS-TAg mice injected with AdCre developed undifferentiated ovarian tumors with mixed epithelial and stromal components and some features of sex cord stromal tumors. Treatment with VCD before or after AdCre injection yielded tumors of similar histology, but with the unique appearance of Sertoli cell nests. In mice treated with VCD before the induction of tumorigenesis, the ovarian tumors tended to grow more slowly. The human ovarian cancer cell lines SKOV3 and OVCAR3 responded similarly to increased levels of gonadotropins in a second model of menopause, growing more slowly in ovariectomized mice compared with cycling controls.
  
  
  CONCLUSIONS
  These results suggest that follicle depletion and increased gonadotropin levels can alter the histology and the rate of growth of ovarian tumors.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Laviolette
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ethier
authors.forename: Mary K
authors.initials: MK
authors.lastname: Senterman
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Devine
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Vanderhyden
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D053138:Cyclohexenes / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008593:Menopause; D051379:Mice; D008822:Mice, Transgenic; D006080:Ovarian Follicle / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000473:pathology*; D012707:Sertoli Cell Tumor / Q000139:chemically induced / Q000473:pathology*; D013539:Simian virus 40; D014753:Vinyl Compounds / Q000633:toxicity
chemical_list: D053138:Cyclohexenes; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone