kt-5720 and Urinary-Bladder-Neoplasms

Cyclic AMP (cAMP) has been implicated in the regulation of movement of certain cultured cell types. We have studied the effects of cAMP on epithelial cell motility using serum-free NBT-II cells, derived from a rat bladder carcinoma. The random movement of these cells on type I collagen was reduced upon elevation of intracellular cAMP by several means and this effect was reversible. Alterations in the organization of the cytoskeletal proteins F-actin and alpha-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, pretreatment of cells with KT5720, a cAMP-dependent protein kinase (PKA)-specific inhibitor, prevented the dibutyryl cAMP-induced reduction in cell movement as well as the associated cytoskeletal changes. These results suggest that elevation of PKA is responsible for the observed effects on cell motility and cytoskeletal reorganization and demonstrate a role for PKA in the regulation of cell motility in this system.

Topics: Actinin; Actins; Animals; Bucladesine; Carbazoles; Cell Membrane; Cell Movement; Cholera Toxin; Cyclic AMP; Cytoskeleton; Indoles; Protein Kinase Inhibitors; Protein Kinases; Pyrroles; Rats; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Virulence Factors, Bordetella