EXPRESSION OF APOPTOSIS-RELATED PROTEINS IN THYROID-TUMORS AND THYROID-CARCINOMA CELL-LINES

Whereas in normal human thyroid tissue total cell mass is maintained b y a balance between cell proliferation and apoptosis, the programmed c ell death, in thyroid tumors this equilibrium is disrupted. In tumor c ells, an augmented proliferation rate is no longer counterbalanced by an equally enhanced apoptosis resulting in an increased netto growth r ate. To investigate regulation of apoptosis in thyroid tumors, we anal yzed the expression of apoptosis-related proteins of the bcl-2 family in human thyroid tissues and in the human thyroid carcinoma cell lines FTC 133, HTC, HTC-TSHr and HTh74. In comparison to normal tissue, we detected an increased expression of the anti-apoptotic protein bcl-2 i n adenomas, whereas follicular carcinomas showed various expression of bcl-2 with decreased levels in 32% of cases. Bclx(L) expression was c omparable in all tissues examined. The pro-apoptotic protein bax was e xpressed at lower levels in carcinomas than in adenomas, whereas bak a nd bclx(S) were expressed in the same order of magnitude in all tissue s examined. In contrast, thyroid carcinoma cell lines exhibited a rela tively strong expression of bclx(L), but a weak expression of bcl-2. I n all four cell lines, the amounts of the pro-apoptotic proteins bax, bak and bclx(S) were higher than in most tumor tissues. Our data show that in thyroid tumors expression of members of the bcl-2 protein fami ly is not uniform. Rather, the expression pattern of pro- and anti-apo ptotic proteins in thyroid tumors is heterogeneous. This may, at least in part, reflect the futile attempt of tumor cells to counterbalance the action of growth-promoting factors in thyroid tumorigenesis.