Impairment of ATP-induced Ca super(2+)-signalling in human thyroid cancer cells

• Published in: Molecular and cellular endocrinology 1997-09, Vol.133 (1), p.33-39
• Main Authors: Schoefl, C, Roessig, L, Mader, T, Boerger, J, Poetter, E, von zur Muehlen, A, Brabant, G
• Format: Article
• Language: English
• ISSN: 0303-7207

Extracellular nucleotides like ATP that activate the Ca super(2+)-phosphatidylinositol (PI) signalling pathway have been suggested to participate in the regulation of normal human thyroid function. We examined, whether P sub(2y)-purinergic receptors are expressed on human thyroid cancer cells and whether post-receptor Ca super(2+) signalling is altered by malignant transformation. Extracellular ATP caused a biphasic increase in cytosolic free Ca super(2+) ([Ca super(2+)] sub(i)) in normal human thyrocytes and in human follicular (FTC) and papillary (PTC) thyroid carcinoma cells. In FTC and PTC cell lines the dose-response curves for ATP-induced changes in [Ca super(2+)] sub(i) were shifted to the right when compared with normal thyrocytes, whereas in undifferentiated thyroid carcinoma (UTC) cells even high concentrations of ATP (500 mu M) failed to stimulate a rise in [Ca super(2+)] sub(i). By contrast, ATP stimulated inositol 1,4,5-trisphosphate (IP sub(3)) formation and capacitative Ca super(2+) entry was operational as judged by thapsigargin in normal thyrocytes and all thyroid cancer cells. Thus, P sub(2y)-purinergic receptors are expressed on thyroid tumor cells independent of degree of differentiation. In UTC cells, however, impairment in the Ca super(2+)-phosphatidylinositol (PI) signalling cascade occurs distal to the formation of IP sub(3) and proximal to the activation of capacitative Ca super(2+) entry. Disturbed ATP-induced Ca super(2+)-signalling and alterations in the Ca super(2+)-PI signalling cascade may contribute to decreased expression or loss of specific thyroid functions in thyroid cancer cells.