Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer

J. Kleeff, X. Shi, H. P. Bode, K. Hoover, S. Shrikhande, P. J. Bryant, Murray Korc, M. W. Büchler, H. Friess

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 ductlike 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.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalPancreas
Volume23
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Zonula Occludens-1 Protein
Pancreatic Neoplasms
Adenocarcinoma
Chronic Pancreatitis
Pancreas
Staining and Labeling
Tight Junction Proteins
Confocal Microscopy
Cell Communication
Northern Blotting
Cell Differentiation
Membrane Proteins
Lymph Nodes
Western Blotting
Cell Proliferation
Cell Line
Messenger RNA

Keywords

  • Chronic pancreatitis
  • MAGUK
  • Pancreatic cancer
  • Pancreatic ductal adenocarcinoma
  • Tight junction
  • Tumor suppressor

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

Cite this

Kleeff, J., Shi, X., Bode, H. P., Hoover, K., Shrikhande, S., Bryant, P. J., ... Friess, H. (2001). Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer. Pancreas, 23(3), 259-265. https://doi.org/10.1097/00006676-200110000-00006

Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer. / Kleeff, J.; Shi, X.; Bode, H. P.; Hoover, K.; Shrikhande, S.; Bryant, P. J.; Korc, Murray; Büchler, M. W.; Friess, H.

In: Pancreas, Vol. 23, No. 3, 2001, p. 259-265.

Research output: Contribution to journalArticle

Kleeff, J, Shi, X, Bode, HP, Hoover, K, Shrikhande, S, Bryant, PJ, Korc, M, Büchler, MW & Friess, H 2001, 'Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer', Pancreas, vol. 23, no. 3, pp. 259-265. https://doi.org/10.1097/00006676-200110000-00006
Kleeff, J. ; Shi, X. ; Bode, H. P. ; Hoover, K. ; Shrikhande, S. ; Bryant, P. J. ; Korc, Murray ; Büchler, M. W. ; Friess, H. / Altered expression and localization of the tight junction protein ZO-1 in primary and metastatic pancreatic cancer. In: Pancreas. 2001 ; Vol. 23, No. 3. pp. 259-265.
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