Different Growth Control of the Two Human Thyroid Cell Lines of Adenomatous Goiter and Papillary Carcinoma

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Abstract
To study the growth control of human thyroid cells in different stages of differentiation, we established two human thyroid cell lines of adenomatous goiter and papillary carcinoma. A 59-year-old female patient with adenomatous goiter was operated in September 1991, and a 27-year-old female patient with papillary carcinoma in May 1990. The thyroid cell lines were established by successive passage without cellular or genetic manipulations such as fusing other cell lines or oncogenic viral infection. These cell lines, human adenomatous goiter cells (hAG) and human papillary thyroid carcinoma cells (hPTC), exhibited a flattened polygonal shape and proliferated as a monolayer in cell culture. The doubling time of the hAG cells was 60 h in Ham's F12 medium supplemented with 10% fetal bovine serum, and that of the hPTC cells, 18 h in the same medium. Both cell lines expressed mRNA for TSH receptor and secreted cAMP into the medium during incubation with thyrotropin (TSH) at concentrations as low as 0.01 mU/mL. The effects of activators of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (TK), and estradiol (E2) on proliferation of the hAG cells and the hPTC cells were assessed by measuring cellular DNA content in 24-well plates with diaminobenzoic acid. TSH stimulated proliferation of the hAG cells, but it inhibited proliferation of the hPTC cells. Since TSH activates two signaling pathways, the adenyl cyclase-PKA system and phospholipase C-PKC system, we tested effects of dibutylyl cAMP (dBC) and phorbol myristate 13-acetate (PMA), separately. dBC stimulated proliferation of the hAG cells, but it inhibited that of the hPTC cells. PMA stimulated growth of the hAG cells, but it did not affect replication of the hPTC cells. Epidermal growth factor, basic fibroblast growth factor, and insulin-like growth factor-1, all of which bind to their respective receptors with TK activity, stimulated growth of the hAG cells and the hPTC cells. E2 stimulated growth of the hAG cells and the hPTC cells; progesterone did not affect proliferation of the hAG cells and the hPTC cells. In summary, we established the two human thyroid cell lines of adenomatous goiter and papillary carcinoma. Activation of PKA and PKC stimulated proliferation of the hAG cells, but activation of PKA inhibited growth of the hPTC cells and activation of PKC did not affect replication of the hPTC cells. Activation of TK and stimulation by E2 promoted proliferation of both the hAG cells and the hPTC cells. Our results suggest that in contrast to the growth of benign thyroid nodules, growth of some thyroid carcinomas is not promoted by TSH.

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