Breadcrumb

Center for Advanced Preclinical Research: Serous Epithelial Ovarian Cancer

Genetically Engineered Mouse (GEM) Model

  • Developed in house
    Image
    Scan showing serous epithelial ovarian carcinoma in a genetically engineered mouse model
    Scan showing SEOC in a GEM model
  • Genetic aberrations:
    • Inactivation of Rb tumor suppression (via K18-T121 transgene)
    • Tp53 loss or mutation (R172H)
    • Brca1 or Brca2 loss
  • Induction by injection of adenovirus expressing Cre recombinase under the ovarian bursa
  • Pathology:
    • Serous epithelial ovarian cancer (SEOC)
    • Peritoneal carcinomatosis
    • Distal metastases (lung, liver)
    • Ascites
  • Latency: 8-12 months (high grade tumor)
  • Metabolomic and gene expression profile aligns with human SEOC
  • Pertubation of Rb, p53 and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer (Szabova et al.,┬áCancer Research 2012)

Orthotopic Allograft Model

Image
Scan showing serous epithelial ovarian cancer in an orthotopic allograft mouse model
Scan showing SEOC in an orthotopic allograft mouse model
  • Derived from genetically engineered mouse ovarian tumors
  • Ovarian tumor transplant to wild-type recipient mice
  • Genetic aberrations:
    • Inactivation of Rb tumor suppression (via K18-T121 transgene)
    • Tp53 loss or mutation (R172H)
    • Bra1 or Brca2 loss
  • Pathology:
    • Serous epithelial ovarian cancer (SEOC)
    • Peritoneal carcinomatosis
    • Distal metastases (lung, liver)
    • Ascites
  • Latency: 1-3 months
  • Molecular profile aligns with human SEOC
  • Ultrasound imaging
  • Differential response to therapeutics in Brca1-deficient versus Brca1 wild-type tumors
  • Pathway-specific engineered mouse allograft models functionally recapitulate human serous epithelial ovarian cancer (Szabova et al., PloS One 2014)