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

Abstract

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.

Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells

“…The literature regarding the two described ZO-2 isoforms is extremely scarce and reports that the expression of specific ZO-2 isoforms is dependent on the cell type suggest different biological functions for these two molecules [7]. In agreement with our observations, Chlenski et al [6] have not detected isoform A in pancreatic adenocarcinoma when compared to normal tissues, while isoform C was detected in all tumor samples. Thus, our results suggest that a diminution of the ZO-2A form could be specifically involved in the process of tumor progression of bronchopulmonary carcinomas.…”

“…ZO-2C protein is 23 amino acids shorter at the N-terminus than ZO-2A [6,7]. Three others forms have also been described, two derived from form A and one from form C. However little is known about the potential functional differences between these isoforms.…”

Loss of occludin leads to the progression of human breast cancer

“…Certain studies have suggested that some of the cell adhesion and cytoskeletal proteins could subserve an additional and important function, namely the suppression of the malignant phenotype of cells in tumourigenesis (39). Whilst the barrier and fence functions of TJs have been well appreciated in the past, it was not till later that the concept of the TJ as a complex, multiprotein structure with roles in other cellular processes such as cell polarity, proliferation and differentiation, was recognised (40).…”

Tight junctions at a glance

“…For example, the expression levels of ZO-1 and ZO-2 are dysregulated in different types of cancers and, in the case of breast cancer, low expression of ZO-1 has been correlated with a poor prognosis (Chlenski et al, 2000;Chlenski et al, 1999;Hoover et al, 1998;Kleeff et al, 2001;Martin et al, 2004;Morita et al, 2004;Resnick et al, 2005;Takai et al, 2005). Similarly, several junctional scaffolding proteins are bound and inactivated by viral oncogenes (Glaunsinger et al, 2001;Latorre et al, 2005).…”