GROWTH-INHIBITION OF NEW HUMAN THYROID-CARCINOMA CELL-LINES BY ACTIVATION OF ADENYLATE-CYCLASE THROUGH THE BETA-ADRENERGIC-RECEPTOR

In normal thyroid cells, the TSH-adenylate cyclase system plays a pivo tal role in controlling growth and differentiation. However, the role of this system in the growth of thyroid carcinoma is not well understo od. To investigate this subject, we have established four new human th yroid carcinoma cell lines, designated BHP 2-7, 7-13, 10-3, and 18-21, from different patients. Northern gel analysis revealed that all of t hese cell lines expressed Pax-8 messenger ribonucleic acid; additional ly, only BHP 18-21 cells expressed TTF-1 messenger ribonucleic acid. T hese cells were treated with various concentrations of 8-bromo-cAMP, f orskolin, TSH, and adrenergic receptor agonist (norepinephrine, epinep hrine, and isoproterenol), Cell proliferation was assessed by [H-3]thy midine incorporation and cell number. In these human thyroid carcinoma cell lines, the addition of 8-bromo-cAMP reduced [H-3]thymidine incor poration at a concentration of 10 mu mol/L. Forskolin (0.1-10 mu mol/L ) significantly induced cAMP accumulation, decreased [H-3]thymidine in corporation, and reduced cell number in a dose-dependent manner. Conve rsely, TSH (0.01-1 mU/mL) did not affect the accumulation of cAMP or c ell growth. We found that adrenergic receptor agonists induced the acc umulation of cAMP and inhibited cell growth. The rank of potency was i soproterenol > epinephrine >> norepinephrine. The binding studies of [ H-3]CGP-12177, a specific beta-adrenergic agonist, revealed that these new thyroid carcinoma cells had beta-adrenergic receptors. These resu lts indicate that cAMP inhibits the growth of some human thyroid carci noma cells, and that cAMP production is regulated through beta-adrener gic receptor-mediated pathways, but not through TSH receptor-mediated pathways.