THE HUMAN PANCREATITIS-ASSOCIATED PROTEIN (PAP)-ENCODING GENE GENERATES MULTIPLE TRANSCRIPTS THROUGH ALTERNATIVE USE OF 5' EXONS

The nucleotide (nt) sequence of the human cDNA encoding PAP, a pancreatic secretory protein induced during acute pancreatitis, was found to be identical with that of a gene activated in human primary hepatocellular cancer, designated HIP. To obtain insight into the expression of PAP/HIP, we characterized the gene organization, especially focusing on the 5'-flanking region, and found that it spans about 3 kb and is composed of six exons, Exon 1 encodes the 5'-noncoding sequence and exon 2 consists of three miniexons, 2a, 2b and 2c; the common exon 2c encodes the sequence including the start codon. Analysis by RT-PCR revealed the presence of at least three different types of 5'-ends of human PAP/HIP transcripts which were derived from alternative use of 5'-exons. Although all three types of transcripts were expressed in both normal small intestine and pancreas, their gene expression was increased ectopically in gastric cancer, hepatocellular cancer and pancreatic acinar cell carcinoma, Furthermore, significant differences among the transcript types were detected between normal and tumor tissues, and especially between gastric and hepatocellular cancers, suggesting that PAP/HIP expression may vary with differences in 5'-alternative splicing.