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 staurosporine, 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%). Staurosporine did not reverse EGF stimulation. The tyrosine kinase antagonist genistein 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.
Hoelting
T
T
Surgical Service, Veterans Affairs Medical Center, San Francisco, CA.
Tezelman
S
S
Siperstein
A E
AE
Duh
Q Y
QY
Clark
O H
OH
D000470:Alkaloids / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D009361:Neoplasm Invasiveness; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D010566:Virulence Factors, Bordetella; D004815:Epidermal Growth Factor; D013972:Thyrotropin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate