Clinical cancer research : an official journal of the American Association for Cancer Research · 2004
Epithelial-cadherin and beta-catenin expression changes in pancreatic intraepithelial neoplasia.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Al-Aynati Maamoun M, Radulovich Nikolina, Riddell Robert H, Tsao Ming-Sound
Аннотация
PURPOSE: Cadherins and associated catenins are important mediators of epithelial cell-cell adhesion, as well as the Wnt-signaling pathway. Significant changes in their expression or structure have been implicated in malignancy. This study aimed to investigate the epithelial-cadherin (E-cadherin) and beta-catenin expression changes during multistage, pancreatic ductal carcinogenesis.
EXPERIMENTAL DESIGN: Ninety-four Whipple resection specimens were retrieved from the surgical pathology files of the University Health Network (Toronto, Canada), from which tissue microarray blocks containing 36 pancreatic ductal adenocarcinomas, 34 PanIN-1A lesions, 28 PanIN-1B lesions, 27 PanIN-2 lesions, 16 PanIN-3 lesions, and 32 normal ducts were constructed. The E-cadherin, beta-catenin, and the phosphorylated glycogen synthase kinase-3beta of the Wnt/beta-catenin pathway were immunohistochemically evaluated in these duct/PanIN lesions.
RESULTS: There was marked increase in the cytoplasmic E-cadherin expression in PanIN lesions (P < 0.0001) and adenocarcinoma (P = 0.005) compared with normal pancreatic ducts. In contrast, reduced/loss of E-cadherin membranous expression was also significant in ductal adenocarcinoma compared with both the PanIN lesions (P < 0.0001) and normal ducts (P = 0.05). The beta-catenin expression showed significantly more frequent aberrant nuclear localization in high-grade PanIN lesions, particularly PanIN2 and in adenocarcinoma compared with normal ducts or low grade PanIN lesions (P < 0.0001). However, there was a lack of correlation between phospho(Ser9)-glycogen synthase kinase-3beta cytoplasmic expression and beta-catenin aberrant nuclear expression (P = 0.07).
CONCLUSIONS: Aberration in the expression of E-cadherin and its associated beta-catenin is evident in pre-invasive (PanIN) neoplastic pancreatic duct cells, suggesting involvement of pathways leading to beta-catenin stabilization during pancreatic duct cell carcinogenesis.
EXPERIMENTAL DESIGN: Ninety-four Whipple resection specimens were retrieved from the surgical pathology files of the University Health Network (Toronto, Canada), from which tissue microarray blocks containing 36 pancreatic ductal adenocarcinomas, 34 PanIN-1A lesions, 28 PanIN-1B lesions, 27 PanIN-2 lesions, 16 PanIN-3 lesions, and 32 normal ducts were constructed. The E-cadherin, beta-catenin, and the phosphorylated glycogen synthase kinase-3beta of the Wnt/beta-catenin pathway were immunohistochemically evaluated in these duct/PanIN lesions.
RESULTS: There was marked increase in the cytoplasmic E-cadherin expression in PanIN lesions (P < 0.0001) and adenocarcinoma (P = 0.005) compared with normal pancreatic ducts. In contrast, reduced/loss of E-cadherin membranous expression was also significant in ductal adenocarcinoma compared with both the PanIN lesions (P < 0.0001) and normal ducts (P = 0.05). The beta-catenin expression showed significantly more frequent aberrant nuclear localization in high-grade PanIN lesions, particularly PanIN2 and in adenocarcinoma compared with normal ducts or low grade PanIN lesions (P < 0.0001). However, there was a lack of correlation between phospho(Ser9)-glycogen synthase kinase-3beta cytoplasmic expression and beta-catenin aberrant nuclear expression (P = 0.07).
CONCLUSIONS: Aberration in the expression of E-cadherin and its associated beta-catenin is evident in pre-invasive (PanIN) neoplastic pancreatic duct cells, suggesting involvement of pathways leading to beta-catenin stabilization during pancreatic duct cell carcinogenesis.
Предметные рубрики MeSH
AdenocarcinomaCadherinsCarcinoma in SituCell AdhesionCell Line, TumorCytoplasmCytoskeletal ProteinsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansImmunohistochemistryOligonucleotide Array Sequence AnalysisPancreatic NeoplasmsPhosphorylationRNA, MessengerReverse Transcriptase Polymerase Chain ReactionSignal TransductionTrans-Activatorsbeta Catenin