Growth inhibition of new human thyroid carcinoma cell lines by activation of adenylate cyclase through the beta-adrenergic receptor.

Abstract

In normal thyroid cells, the TSH-adenylate cyclase system plays a pivotal role in controlling growth and differentiation. However, the role of this system in the growth of thyroid carcinoma is not well understood. To investigate this subject, we have established four new human thyroid carcinoma cell lines, designated BHP 2-7, 7-13, 10-3, and 18-21, from different patients. Northern gel analysis revealed that all of these cell lines expressed Pax-8 messenger ribonucleic acid; additionally, only BHP 18-21 cells expressed TTF-1 messenger ribonucleic acid. These cells were treated with various concentrations of 8-bromo-cAMP, forskolin, TSH, and adrenergic receptor agonist (norepinephrine, epinephrine, and isoproterenol). Cell proliferation was assessed by [3H]thymidine incorporation and cell number. In these human thyroid carcinoma cell lines, the addition of 8-bromo-cAMP reduced [3H]thymidine incorporation at a concentration of 10 mumol/L. Forskolin (0.1-10 mumol/L) significantly induced cAMP accumulation, decreased [3H]thymidine incorporation, and reduced cell number in a dose-dependent manner. Conversely, TSH (0.01-1 mU/ mL) did not affect the accumulation of cAMP or cell growth. We found that adrenergic receptor agonists induced the accumulation of cAMP and inhibited cell growth. The rank of potency was isoproterenol > epinephrine > > norepinephrine. The binding studies of [3H]CGP-12177, a specific beta-adrenergic agonist, revealed that these new thyroid carcinoma cells had beta-adrenergic receptors. These results indicate that cAMP inhibits the growth of some human thyroid carcinoma cells, and that cAMP production is regulated through beta-adrenergic receptor-mediated pathways, but not through TSH receptor-mediated pathways.

• Authors: K Ohta, X P Pang, L Berg, J M Hershman
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 82 Issue 8 Pg. 2633-8 (Aug 1997) ISSN: 0021-972X [Print] United States
• PMID: 9253346 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenergic beta-Agonists
• DNA, Neoplasm
• DNA-Binding Proteins
• NKX2-1 protein, human
• Nkx2-1 protein, rat
• Nuclear Proteins
• PAX8 Transcription Factor
• PAX8 protein, human
• Paired Box Transcription Factors
• Pax8 protein, rat
• Propanolamines
• RNA, Messenger
• Receptors, Adrenergic, beta
• TTF1 protein, human
• Thyroid Nuclear Factor 1
• Trans-Activators
• Transcription Factors
• Colforsin
• Cyclic AMP
• Adenylyl Cyclases
• CGP 12177

Topics

• Adenylyl Cyclases (metabolism)
• Adrenergic beta-Agonists (metabolism)
• Adult
• Animals
• Cell Division
• Colforsin (pharmacology)
• Cyclic AMP (metabolism)
• DNA, Neoplasm (biosynthesis)
• DNA-Binding Proteins (genetics)
• Enzyme Activation
• Female
• Humans
• Nuclear Proteins
• PAX8 Transcription Factor
• Paired Box Transcription Factors
• Propanolamines (metabolism)
• RNA, Messenger (analysis)
• Rats
• Receptors, Adrenergic, beta (physiology)
• Thyroid Neoplasms (pathology)
• Thyroid Nuclear Factor 1
• Trans-Activators (genetics)
• Transcription Factors
• Tumor Cells, Cultured