GROWTH-REGULATION OF THE HUMAN PAPILLARY THYROID-CANCER CELL-LINE BY PROTEIN-TYROSINE KINASE AND CAMP-DEPENDENT PROTEIN-KINASE

We established a cell line (hPTC) from the tissue of papillary thyroid cancer surgically excised from a 27-year old female patient. Synthesi s of cAMP by the hPTC cells was stimulated by TSH. This cell line has continued to divide as a monolayer in a tissue culture for three years . We assessed growth regulation of the hPTC cells by protein tyrosine kinase and cAMP-dependent protein kinase by measuring the DNA content of the hPTC cells in 24-well plates with 3, 5-diaminobenzoic acid afte r incubation in various growth factors. Basic fibroblast growth factor (FGF), epidermal growth factor (EGF), and insulin-like growth factor- 1 (IGF-1), all of which bind to their respective receptors with tyrosi ne kinase activity, stimulated DNA synthesis in the hPTC cells. Neutra lizing antibodies to basic FGF and EGF suppressed the growth stimulati on by basic FGF and EGF, respectively. Genistein, a specific protein t yrosine kinase inhibitor, inhibited proliferation of the hPTC cells. O n the other hand, thyrotropin, dibutyryl cAMP (dBC) and forskolin inhi bited proliferation. KT5720, a specific cAMP-dependent protein kinase inhibitor, restored the growth of the hPTC cells even in the presence of dBC. This study shows that stimulation of the protein tyrosine kina se activity by basic FGF, EGF, and IGF-1 promoted DNA replication by t he human thyroid cancer cell line. However, activation of the cAMP-dep endent protein kinase inhibited proliferation of this cell line.