Expression of specific tau exons in normal and tumoral pancreatic acinar cells.
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.
Vanier
M T
MT
INSERM U.381, 3 avenue Molière, 67200 Strasbourg, France.
Neuville
P
P
Michalik
L
L
Launay
J F
JF
D000681:Amylases / Q000378:metabolism; D000818:Animals; D003001:Cloning, Molecular; D017931:DNA Primers; D005091:Exons / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D008870:Microtubules / Q000502:physiology; D008969:Molecular Sequence Data; D010179:Pancreas / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010190:Pancreatic Neoplasms; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics*
D017931:DNA Primers; D012333:RNA, Messenger; D016875:tau Proteins; D000681:Amylases