Induction of ovarian cancer by defined multiple genetic changes in a mouse model system

Cancer Cell. 2002 Feb;1(1):53-62. doi: 10.1016/s1535-6108(01)00002-2.

Abstract

We have developed a mouse model for ovarian carcinoma by using an avian retroviral gene delivery technique for the introduction of multiple genes into somatic ovarian cells of adult mice. Ovarian cells from transgenic mice engineered to express the gene encoding the avian receptor TVA were efficiently infected in vitro with multiple vectors carrying coding sequences for oncogenes and marker genes. When target cells were derived from TVA transgenic mice deficient for p53, the addition of any two of the oncogenes c-myc, K-ras, and Akt were sufficient to induce ovarian tumor formation when infected cells were injected at subcutaneous, intraperitoneal, or ovarian sites. We demonstrated that the ovarian surface epithelium is the precursor tissue for these ovarian carcinomas, and that introduction of oncogenes causes phenotypic changes in the ovarian surface epithelial cells. The induced ovarian tumors in mice resembled human ovarian carcinomas in their rapid progression and intraperitoneal metastatic spread.

Publication types

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

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Alkaline Phosphatase / metabolism
  • Animals
  • Avian Proteins
  • Blotting, Western
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Division / physiology
  • Cell Transformation, Neoplastic
  • Disease Models, Animal*
  • Female
  • Gene Transfer Techniques
  • Genes, myc / genetics*
  • Genes, ras / genetics*
  • Genetic Vectors
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-akt
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Actins
  • Avian Proteins
  • Calcium-Binding Proteins
  • Proto-Oncogene Proteins
  • Receptors, Virus
  • Tumor Suppressor Protein p53
  • Tva receptor
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Alkaline Phosphatase