Purinergic agonist ATP is a comitogen in thyroid FRTL-5 cells.
Several growth factors may stimulate proliferation of thyroid cells. This effect has, in part, been dependent on calcium entry. In the present study using FRTL-5 cells, we show that in addition to its effect on calcium fluxes, ATP acts as a comitogen in these cells. In medium containing 5% serum, but no TSH, ATP stimulated the incorporation of 3H-thymidine in a dose- and time-dependent manner in the cells. At least a 24-h incubation with ATP was necessary to observe the enhanced (30-50%) incorporation of 3H-thymidine and an increased (30%) cell number. The effect of ATP was dependent on insulin in the incubation medium. Furthermore, ATP enhanced the TSH-mediated incorporation of 3H-thymidine. The effect of ATP was apparently mediated via a G-protein dependent mechanism, as no stimulation of thymidine incorporation was observed in cells treated with pertussis toxin. The effect of ATP was not dependent on the activation of protein kinase C (PKC), as ATP was effective in cells with downregulated PKC. ATP rapidly phosphorylated mitogen activated protein (MAP) kinase in FRTL-5 cells. In addition, ATP stimulated the expression of a 62 kDa c-fos dependent protein in a dose- and time-dependent manner. Our results thus suggest that extracellular ATP, in the presence of insulin, may be a cofactor in the regulation of thyroid cell proliferation, probably by phosphorylating MAP kinase and stimulating the expression of c-fos.
Törnquist
K
K
Department of Biosciences, University of Helsinki, Finland.
Ekokoski
E
E
Dugué
B
B
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D004789:Enzyme Activation; D007328:Insulin / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1; D008934:Mitogens / Q000494:pharmacology*; D010741:Phospholipases A / Q000378:metabolism; D010766:Phosphorylation; D011453:Prostaglandins / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011687:Purines / Q000819:agonists*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology
D003470:Culture Media; D007328:Insulin; D008934:Mitogens; D011453:Prostaglandins; D016760:Proto-Oncogene Proteins c-fos; D011687:Purines; D000255:Adenosine Triphosphate; D013972:Thyrotropin; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D010741:Phospholipases A; D002118:Calcium; D013936:Thymidine