Tau is a neuron-specific microtubule-associated protein (MAP) that is required for the development and maintaining neuronal cell polarity. Tau is encoded by a single gene, while its transcript undergoes a complex and regulated alternative splicing. We have recently reported that tau-like MAPs of 48-55 kDa, corresponding to 6 kb mRNA on northern blots, are expressed in pancreatic acinar cells. In the present study, the expression of tau exons in normal and tumoral pancreatic acinar cells was investigated by RT-PCR and cDNA sequencing. Tau isoforms with four tubulin-binding motifs containing either none, one or two N-terminal inserts (exons 2, 3) are indiscriminately expressed in normal and tumoral cells. However, tau transcripts containing the sequence encoded by exon 6 are specifically expressed in pancreatic tumoral cells from exocrine origin. By immunofluorescence and electron microscopy, we have identified in cellular extensions of tumoral cells, tau-decorated microtubules arranged in bundles like those found in neuronal processes. Tau antisense oligonucleotides inhibit the development of these cellular processes and the expression of the 55 kDa tau isoform.