title: Obesity increases tumor aggressiveness in a genetically engineered mouse model of serous ovarian cancer.
abstract: OBJECTIVE
  Obesity is associated with increased risk and worse outcomes for ovarian cancer. Thus, we examined the effects of obesity on ovarian cancer progression in a genetically engineered mouse model of serous ovarian cancer.
  
  
  METHODS
  We utilized a unique serous ovarian cancer mouse model that specifically deletes the tumor suppressor genes, Brca1 and p53, and inactivates the retinoblastoma (Rb) proteins in adult ovarian surface epithelial cells, via injection of an adenoviral vector expressing Cre (AdCre) into the ovarian bursa cavity of adult female mice (KpB mouse model). KpB mice were subjected to a 60% calories-derived from fat in a high fat diet (HFD) versus 10% calories from fat in a low fat diet (LFD) to mimic diet-induced obesity. Tumors were isolated at 6 months after AdCre injection and evaluated histologically. Untargeted metabolomic and gene expression profiling was performed to assess differences in the ovarian tumors from obese versus non-obese KpB mice.
  
  
  RESULTS
  At sacrifice, mice on the HFD (obese) were twice the weight of mice on the LFD (non-obese) (51g versus 31g, p=0.0003). Ovarian tumors were significantly larger in the obese versus non-obese mice (3.7cm(2) versus 1.2cm(2), p=0.0065). Gene expression and metabolomic profiling indicated statistically significant differences between the ovarian tumors from the obese versus non-obese mice, including metabolically relevant pathways.
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Liza
authors.initials: L
authors.lastname: Makowski
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Pei Fen
authors.initials: PF
authors.lastname: Kuan
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.affiliation: Metabolon, Inc., Durham, NC, USA.
authors.forename: Brante P
authors.initials: BP
authors.lastname: Sampey
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Difurio
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; Division of Gynecologic Oncology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: victoria_baejump@med.unc.edu.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Bae-Jump
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055442:Metabolome; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications*; D010051:Ovarian Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*
keywords: Biomarkers; Genomics; Metabolomics; Mouse model; Obesity; Ovarian cancer