The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis

Iris L. Romero, Wooseok Lee, Anirban K. Mitra, Ilyssa O. Gordon, Yan Zhao, Payton Leonhardt, Carla V. Penicka, Keeley L. Mui, Thomas N. Krausz, Geoffrey L. Greene, Ernst Lengyel

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9 Scopus citations

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)134-141
Number of pages8
JournalGynecologic oncology
Volume124
Issue number1
DOIs
StatePublished - Jan 1 2012

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Keywords

  • 17β-estradiol
  • Genetic mouse model
  • Hormone replacement therapy
  • Ovarian cancer
  • Selective estrogen receptor modulators

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Romero, I. L., Lee, W., Mitra, A. K., Gordon, I. O., Zhao, Y., Leonhardt, P., Penicka, C. V., Mui, K. L., Krausz, T. N., Greene, G. L., & Lengyel, E. (2012). The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis. Gynecologic oncology, 124(1), 134-141. https://doi.org/10.1016/j.ygyno.2011.08.026