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. CONCLUSION: 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.
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. CONCLUSION: 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: R S Price; D A Cavazos; R E De Angel; S D Hursting; L A deGraffenried Journal: Prostate Cancer Prostatic Dis Date: 2012-02-14 Impact factor: 5.554
Authors: Alan A Arslan; Kathy J Helzlsouer; Charles Kooperberg; Xiao-Ou Shu; Emily Steplowski; H Bas Bueno-de-Mesquita; Charles S Fuchs; Myron D Gross; Eric J Jacobs; Andrea Z Lacroix; Gloria M Petersen; Rachael Z Stolzenberg-Solomon; Wei Zheng; Demetrius Albanes; Laufey Amundadottir; William R Bamlet; Aurelio Barricarte; Sheila A Bingham; Heiner Boeing; Marie-Christine Boutron-Ruault; Julie E Buring; Stephen J Chanock; Sandra Clipp; J Michael Gaziano; Edward L Giovannucci; Susan E Hankinson; Patricia Hartge; Robert N Hoover; David J Hunter; Amy Hutchinson; Kevin B Jacobs; Peter Kraft; Shannon M Lynch; Jonas Manjer; Joann E Manson; Anne McTiernan; Robert R McWilliams; Julie B Mendelsohn; Dominique S Michaud; Domenico Palli; Thomas E Rohan; Nadia Slimani; Gilles Thomas; Anne Tjønneland; Geoffrey S Tobias; Dimitrios Trichopoulos; Jarmo Virtamo; Brian M Wolpin; Kai Yu; Anne Zeleniuch-Jacquotte; Alpa V Patel Journal: Arch Intern Med Date: 2010-05-10
Authors: Andrew D Rhim; Emily T Mirek; Nicole M Aiello; Anirban Maitra; Jennifer M Bailey; Florencia McAllister; Maximilian Reichert; Gregory L Beatty; Anil K Rustgi; Robert H Vonderheide; Steven D Leach; Ben Z Stanger Journal: Cell Date: 2012-01-20 Impact factor: 41.582
Authors: Seung-Mo Hong; Ang Li; Kelly Olino; Christopher L Wolfgang; Joseph M Herman; Richard D Schulick; Christine Iacobuzio-Donahue; Ralph H Hruban; Michael Goggins Journal: Mod Pathol Date: 2011-05-06 Impact factor: 7.842