title: The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis.
abstract: OBJECTIVE
  To test if estrogen promotes carcinogenesis in vitro and in a genetic mouse model of ovarian cancer and whether its effects can be inhibited by a novel selective estrogen receptor modulator (SERM), bazedoxifene.
  
  
  METHODS
  Bazedoxifene was synthesized and it was confirmed that the drug abrogated the uterine stimulatory effect of 17β-estradiol in mice. To determine if hormones alter tumorigenesis in vivo LSL-K-ras(G12D/+)Pten(loxP/loxP) mice were treated with vehicle control, 17β-estradiol or bazedoxifene. Hormone receptor status of a cell line established from LSL-K-ras(G12D/+)Pten(loxP/loxP) mouse ovarian tumors was characterized using Western blotting and immunohistochemistry. The cell line was treated with hormones and invasion assays were performed using Boyden chambers and proliferation was assessed using MTT assays.
  
  
  RESULTS
  In vitro 17β-estradiol increased both the invasion and proliferation of ovarian cancer cells and bazedoxifene reversed these effects. However, in the genetic mouse model neither treatment with 17β-estradiol nor bazedoxifene changed mean tumor burden when compared to treatment with placebo. The mice in all treatment groups had similar tumor incidence, metastatic nodules and ascites.
  
  
  CONCLUSIONS
  While 17β-estradiol increases the invasion and proliferation of ovarian cancer cells, these effects do not translate into increased tumor burden in a genetic mouse model of endometrioid ovarian cancer. Likewise, while the SERM reversed the detrimental effects of estrogen in vitro, there was no change in tumor burden in mice treated with bazedoxifene. These findings demonstrate the complex interplay between hormones and ovarian carcinogenesis.
authors: Department of Obstetrics and Gynecology, Center for Integrative Science, University of Chicago, IL 60637, USA.
authors: Iris L
authors: IL
authors: Romero
authors: WooSeok
authors: W
authors: Lee
authors: Anirban K
authors: AK
authors: Mitra
authors: Ilyssa O
authors: IO
authors: Gordon
authors: Yan
authors: Y
authors: Zhao
authors: Payton
authors: P
authors: Leonhardt
authors: Carla V
authors: CV
authors: Penicka
authors: Keeley L
authors: KL
authors: Mui
authors: Thomas N
authors: TN
authors: Krausz
authors: Geoffrey L
authors: GL
authors: Greene
authors: Ernst
authors: E
authors: Lengyel
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
chemical_list: D004965:Estrogen Antagonists; D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol; C447119:bazedoxifene