Inhibition of process outgrowth by tau antisense oligonucleotide in rat medullary thyroid carcinoma cells

Calcitonin-producing cells (C-cells) are neural crest derived endocrine cel ls with some intrinsic neuronal properties. Two types of protein kinase inh ibitors, H-7 and staurosporin, promoted marked outgrowth of neurite-like pr ocesses in the cells of rat neoplastic C-cell line, rMTC 6-23. The cells sh owed immunoreactivities to both alpha-tubulin and tau proteins in the whole cytoplasm including processes, suggesting that the microtubule cytoskeleto n in the processes is stabilized by tau proteins. To test the possible role of tau proteins in the process outgrowth, the cells were treated with sens e- and antisense-oriented deoxyoligonucleotides encoding regions of the tau sequence that overlap the translation initiation codon. Antisense, but not sense, oligonucleotide treatment reduced tau-immunoreactivity to backgroun d levels, and markedly inhibited H-7- or staurosporin-induced process outgr owth in the cells. These findings have clearly indicated that tau proteins participate in the outgrowth of neuritic processes in rMTC 6-23 cells.