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 norma l pancreatic duct cells that is not expressed in pancreatic duct carcinoma cells, Sequence analysis showed an 88% and 82% identity, respectively, to t he 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 expres sion of various regions of the ZO-2 transcript in normal and neoplastic cel ls 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, de signated 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 w ith ZO-2A, Although ZO-2C was expressed in normal pancreatic cells and a ma jority 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 regulati on within the 23-amino acid residue hi-terminal peptide of ZO-2A, MPVRGDRGF PPRRELSGWLRAPG. (C) 1999 Wiley-Liss, Inc.