Role of K-ras and Pten in the Development of Mouse Models of Endometriosis and Endometrioid Ovarian Cancer

Nat Med. 2005 Jan;11(1):63-70. doi: 10.1038/nm1173. Epub 2004 Dec 26.

Abstract

Epithelial ovarian tumors present a complex clinical, diagnostic and therapeutic challenge because of the difficulty of early detection, lack of known precursor lesions and high mortality rates. Endometrioid ovarian carcinomas are frequently associated with endometriosis, but the mechanism for this association remains unknown. Here we present the first genetic models of peritoneal endometriosis and endometrioid ovarian adenocarcinoma in mice, both based on the activation of an oncogenic K-ras allele. In addition, we find that expression of oncogenic K-ras or conditional Pten deletion within the ovarian surface epithelium gives rise to preneoplastic ovarian lesions with an endometrioid glandular morphology. Furthermore, the combination of the two mutations in the ovary leads to the induction of invasive and widely metastatic endometrioid ovarian adenocarcinomas with complete penetrance and a disease latency of only 7 weeks. The ovarian cancer model described in this study recapitulates the specific tumor histomorphology and metastatic potential of the human disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Endometriosis / genetics*
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Female
  • Mice
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • PTEN Phosphohydrolase
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • ras Proteins / genetics*
  • ras Proteins / metabolism

Substances

  • Tumor Suppressor Proteins
  • Protein Tyrosine Phosphatases
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • ras Proteins