Journal
PANCREAS
Volume 23, Issue 3, Pages 259-265Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00006676-200110000-00006
Keywords
pancreatic cancer; pancreatic ductal adenocarcinoma; chronic pancreatitis; tight junction; MAGUK; tumor suppressor
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Funding
- NCI NIH HHS [CA-66263, CA-40162] Funding Source: Medline
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Introduction: ZO-1 is a tight junction membrane protein that plays a critical role in cell-cell interaction, proliferation, and differentiation. Aim: To localize and evaluate the expression of ZO-1 in the normal human pancreas, in pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreatitis (CP). Methodology and Results: Northern and Western blot analysis revealed ZO-1 expression in all six tested pancreatic cancer cell lines. Expression of ZO-1 mRNA was increased sixfold in PDAC samples in comparison with normal samples (p = 0.04). Confocal microscopy revealed the presence of ZO-1 in the apical and apicolateral areas of ductular cells in the normal pancreas. Similarly, in CP, ZO-1 was localized at apical and apicolateral areas of small proliferating ductular cells and large metaplastic ducts. In PDAC, however, ZO-1 expression was observed irrespective of whether the cancer cells formed duct-like structures or exhibited a diffuse infiltrating pattern. Metastatic pancreatic cancer cells within lymph nodes displayed variable staining patterns, ranging from apical and apicolateral to a diffuse membranous staining. Conclusion: These observations suggest that ZO-1 is overexpressed in PDAC and raise the possibility that this overexpression may confer a metastatic advantage to pancreatic cancer cells.
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