REGULATION OF MOTILITY AND CYTOSKELETAL ORGANIZATION OF RAT BLADDER-CARCINOMA CELLS BY CYCLIC-AMP

Cyclic AMP (cAMP) has been implicated in the regulation of movement of certain cultured cell types. We have studied the effects of cAMP on e pithelial cell motility using serum-free NET-II cells, derived from a rat bladder carcinoma. The random movement of these cells on type I co llagen was reduced upon elevation of intracellular cAMP by several mea ns and this effect was reversible. Alterations in the organization of the cytoskeletal proteins F-actin and a-actinin occurred concurrently with the reduction in motility, and the arrangement of these proteins resembled that seen in non-motile cells on glass. In addition, pretrea tment of cells with KT5720, a cAMP-dependent protein kinase (PKA)-spec ific inhibitor, prevented the dibutyryl cAMP-induced reduction in cell movement as well as the associated cytoskeletal changes. These result s suggest that elevation of PKA is responsible for the observed effect s on cell motility and cytoskeletal reorganization and demonstrate a r ole for PKA in the regulation of cell motility in this system. (C) 199 4 Wiley-Liss, Inc.