Influence of thyreotropin on mechanisms of apoptosis and radiation resistance of thyroid carcinoma cells

1589 Objectives Higher concentrations of thyreotropin (TSH) have to be considered as an exogenic stress factor. Using two poorly differentiated thyroid carcinoma cell lines we examined the influence of such a high concentration on molecules that act in a pro- and antiapoptotic manner. Methods The ML-1 and FTC-133 cell line were investigated. Bcl-2, fas, p53, bax and caspase-3 were determined (flow cytometry and western blot) after stimulation for 72 h, 2 and 4 weeks with 60 mU/l TSH. Apoptosis was induced by in vitro irradiation with 30 Gy X-rays. Apoptosis was evaluated native, 2 d and 4 d after irradiation by flow cytometry with FITC-labeled annexin V. Results Expression of bcl-2 was influenced extensively under the influence of TSH. Based on the basic value (ML-1 15%, FTC-133 10%) a reduction to 2% and 3% was detectable with an increase after 4d. In both cell lines caspase-3 showed a clear decrease that accelerated in the course of the study. Under stimulation with TSH p53 showed an obvious increase in FTC-133 cells. Stimulation with TSH caused a change of the native rate of apoptosis in ML-1 cells and an increasing radiation resistance in both cell lines (p Conclusions High concentrations of TSH lead to considerable changes in the expression of molecules that act in a pro- and antiapoptotic manner. The increased radiation resistance under stimulation with thyreotropin is a sign of the clinical relevance. Because this effect is detectable in two different cell lines one could expect that other thyroid carcinoma cell lines will show similar reactions.