Tight junction protein zo‐2 is differentially expressed in normal pancreatic ducts compared to human pancreatic adenocarcinoma

Differential display of hamster mRNA identified a fragment present in normal pancreatic duct cells that is not expressed in pancreatic duct carcinoma cells. Sequence analysis showed an 88% and 82% identity, respectively, to the cDNA of the canine and human tight junction zo‐2 gene. Semi‐quantitative RT‐PCR analysis of human ZO‐2 revealed a striking difference in the expression of various regions of the ZO‐2 transcript in normal and neoplastic cells and the presence of an abnormality at the 5′‐end of mRNA. RACE analysis identified 2 human ZO‐2 mRNAs that encode proteins of different lengths, designated as ZO‐2A and ZO‐2C. The difference between the 2 forms of ZO‐2 is the absence of 23 amino acid residues at the N terminus of ZO‐2C compared with ZO‐2A. Although ZO‐2C was expressed in normal pancreatic cells and a majority of neoplastic tissues analyzed, ZO‐2A was undetectable except in one case in all of the pancreatic adenocarcinomas analyzed. This suggests the presence of a yet to be identified motif important for cell‐growth regulation within the 23–amino acid residue N‐terminal peptide of ZO‐2A, MPVRGDRGFPPRRELSGWLRAPG. Int. J. Cancer 82:137–144, 1999. © 1999 Wiley‐Liss, Inc.

[1]  L. Gu,et al.  ZO-3, a Novel Member of the MAGUK Protein Family Found at the Tight Junction, Interacts with ZO-1 and Occludin , 1998, The Journal of cell biology.

[2]  Paul Horton,et al.  Better Prediction of Protein Cellular Localization Sites with the it k Nearest Neighbors Classifier , 1997, ISMB.

[3]  A. Ben-Ze'ev,et al.  Cytoskeletal and adhesion proteins as tumor suppressors. , 1997, Current opinion in cell biology.

[4]  James M. Anderson,et al.  The SH3 domain of the tight junction protein ZO‐1 binds to a serine protein kinase that phosphorylates a region C‐terminal to this domain , 1996, FEBS letters.

[5]  W. Gallin,et al.  The Tight Junction Protein ZO-2 Contains Three PDZ (PSD-95/Discs-Large/ZO-1) Domains and an Alternatively Spliced Region , 1996, The Journal of Biological Chemistry.

[6]  B. Keon,et al.  Symplekin, a novel type of tight junction plaque protein , 1996, The Journal of cell biology.

[7]  M. Tsao,et al.  Long-term culture and immortalization of epithelial cells from normal adult human pancreatic ducts transfected by the E6E7 gene of human papilloma virus 16. , 1996, The American journal of pathology.

[8]  B. Geiger,et al.  Suppression of tumorigenicity by plakoglobin: an augmenting effect of N- cadherin , 1996, The Journal of cell biology.

[9]  T. Ayoubi,et al.  Regulation of gene expression by alternative promoters , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[11]  M. Takeichi,et al.  Increased cell-substratum adhesion, and decreased gelatinase secretion and cell growth, induced by E-cadherin transfection of human colon carcinoma cells. , 1995, Oncogene.

[12]  G. Berx,et al.  Transition from the noninvasive to the invasive phenotype and loss of alpha-catenin in human colon cancer cells. , 1995, Cancer research.

[13]  C. V. Van Itallie,et al.  Zonula occludens (ZO)-1 and ZO-2: membrane-associated guanylate kinase homologues (MAGuKs) of the tight junction. , 1995, Biochemical Society transactions.

[14]  M. Mori,et al.  Development of the blood-retinal barrier in vitro: formation of tight junctions as revealed by occludin and ZO-1 correlates with the barrier function of chick retinal pigment epithelial cells. , 1995, Experimental eye research.

[15]  S. Hubchak,et al.  Multiple genetic alterations in hamster pancreatic ductal adenocarcinomas. , 1995, Cancer research.

[16]  B. Geiger,et al.  Molecular interactions in the submembrane plaque of cell-cell and cell-matrix adhesions. , 1995, Acta anatomica.

[17]  M. Koenig,et al.  The Friedreich ataxia region: characterization of two novel genes and reduction of the critical region to 300 kb. , 1994, Human molecular genetics.

[18]  W. Birchmeier,et al.  Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. , 1994, Biochimica et biophysica acta.

[19]  D. Goodenough,et al.  Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein , 1994, The Journal of cell biology.

[20]  P. Bryant,et al.  Drosophila in cancer research: the first fifty tumor suppressor genes , 1994, Journal of Cell Science.

[21]  M. Itoh,et al.  Occludin: a novel integral membrane protein localizing at tight junctions , 1993, The Journal of cell biology.

[22]  M. Itoh,et al.  Submembranous junctional plaque proteins include potential tumor suppressor molecules , 1993, The Journal of cell biology.

[23]  C. V. Van Itallie,et al.  The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  S. Citi The molecular organization of tight junctions , 1993, The Journal of cell biology.

[25]  D. Kwiatkowski,et al.  Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Mori,et al.  Monoclonal antibody 7H6 reacts with a novel tight junction-associated protein distinct from ZO-1, cingulin and ZO-2 , 1993, The Journal of cell biology.

[27]  B. Geiger,et al.  Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA , 1992, The Journal of cell biology.

[28]  A. Pardee,et al.  Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. , 1992, Science.

[29]  A. Patel,et al.  myc function and regulation. , 1992, Annual review of biochemistry.

[30]  Peter J. Bryant,et al.  The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions , 1991, Cell.

[31]  B. Gumbiner,et al.  Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  M. Groudine,et al.  Control of c-myc regulation in normal and neoplastic cells. , 1991, Advances in cancer research.

[33]  E. Rodriguez-Boulan,et al.  Morphogenesis of the polarized epithelial cell phenotype. , 1989, Science.

[34]  Benjamin Geiger,et al.  Cingulin, a new peripheral component of tight junctions , 1988, Nature.

[35]  James M. Anderson,et al.  Characterization of ZO-1, a protein component of the tight junction from mouse liver and Madin-Darby canine kidney cells , 1988, The Journal of cell biology.

[36]  G. E. Marks The Giemsa-staining centromeres of Nigella damascena. , 1975, Journal of cell science.