title: E-cadherin expression in obesity-associated, Kras-initiated pancreatic ductal adenocarcinoma in mice.
abstract: BACKGROUND
  The epithelial-mesenchymal transition (EMT) is critical in the development of invasive epithelial malignancies. EMT is accelerated by inflammation and results in decreased E-cadherin expression. Diet-induced obesity is an inflammatory state that accelerates pancreatic carcinogenesis; its effect on EMT and E-cadherin expression in the development of pancreatic ductal adenocarcinoma is unclear.
  
  
  METHODS
  Conditional Kras(G12D) mice were fed a control diet or a high-fat, high-calorie diet for 3 or 9 months (n = 10 each). Immunohistochemistry with anti-E-cadherin antibody was performed. E-cadherin expression was characterized by staining intensity, location, and proportion of positive cells. In vitro expression of E-cadherin and Slug in primary pancreatic intraepithelial neoplasia (PanIN) and cancer cells was determined by Western blot.
  
  
  RESULTS
  The HFCD led to increased weight gain in both 3- (15.8 vs 5.6 g, P < .001) and 9-month (19.8 vs 12.9 g, P = .007) mice. No differences in E-cadherin expression among various stages of preinvasive PanIN lesions were found--regardless of age or diet. In invasive cancer, E-cadherin expression was aberrant, with loss of membranous staining and prominent cytoplasmic staining, associated with strong, cytoplasmic expression of β-catenin. In vitro expression of E-cadherin was greatest in primary PanIN cells, accompanied by absent Slug expression. Cancer cell lines demonstrated significantly decreased E-cadherin expression in the presence of upregulated Slug.
  
  
  CONCLUSIONS
  Despite increased pancreatic inflammation and accelerated carcinogenesis, the high-fat, high-calorie diet did not induce changes in E-cadherin expression in PanIN lesions of all stages. Invasive lesions demonstrated aberrant cytoplasmic E-cadherin staining. Loss of normal membranous localization may reflect a functional loss of E-cadherin.
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Alexander P
authors: AP
authors: Stark
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Hui-Hua
authors: HH
authors: Chang
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Xiaoman
authors: X
authors: Jung
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Aune
authors: A
authors: Moro
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Kathleen
authors: K
authors: Hertzer
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Mu
authors: M
authors: Xu
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Andrea
authors: A
authors: Schmidt
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: O Joe
authors: OJ
authors: Hines
authors: Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address: Geibl@mednet.ucla.edu.
authors: Guido
authors: G
authors: Eibl
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D002149:Energy Intake; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D009765:Obesity / Q000150:complications*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)