Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-catenin and PI3K/Pten signaling pathways

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Wu R., Hendrix-Lucas N., Kuick R., Zhai Y., Schwartz D. R., Akyol A., ...More

CANCER CELL, vol.11, no.4, pp.321-333, 2007 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 11 Issue: 4
  • Publication Date: 2007
  • Doi Number: 10.1016/j.ccr.2007.02.016
  • Journal Name: CANCER CELL
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.321-333
  • Hacettepe University Affiliated: Yes


One histologic subtype of ovarian carcinoma, ovarian endonnetrioid adenocarcinorna (OEA), frequently harbors mutations that constitutively activate Wnt/beta-catenin-dependent signaling. We now show that defects in the PI3K/Pten and Wnt/beta-catenin signaling pathways often occur together in a subset of human OEAs, suggesting their cooperation during OEA pathogenesis. Deregulation of these two pathways in the murine ovarian surface epithelium by conditional inactivation of the Pten and Apc tumor suppressor genes results in the formation of adenocarcinomas morphologically similar to human OEAs with 100% penetrance, short latency, and rapid progression to metastatic disease in upwards of 75% of mice. The biological behavior and gene expression patterns of the murine cancers resemble those of human OEAs with defects in the Wnt/beta-catenin and PI3K/Pten pathways.