Thyrotropin Stimulates Invasion and Growth of Follicular Thyroid Cancer Cells via PKC- Rather Than PKA-Activation

The signal transduction of TSH in invasion and growth of FTC 133, a human follicular thyroid cancer cell line, was investigated. TSH (0.01 -1 mIU/ml) stimulated invasion of FTC 133 by 21% and growth by 20% of basal. Cyclic AMP-stimulators and inhibitors had no effect at any concentration. The PKC-agonist TPA enhanced invasion and growth by 15%, whereas stauroporine, a PKC-antagonist, inhibited them by 32% and 60%, respectively. The latter also reversed TSH stimulation. EGF enhanced invasion (42%) and growth of FTC 133 (25%). Stauroporine did not reverse EGF stimulation. The tyrosine kinase antagonist gemstein reversed EGF, but not TSH stimulation. Pertussis toxin inhibited invasion (18%) and growth (22%). Cholera toxin was less inhibitive. We demonstrated for the first time, that TSH stimulates invasion and growth of human thyroid cancer cells in vitro by PKC- rather than PKA-stimulation.