Expression of apoptosis-related proteins in thyroid tumors and thyroid carcinoma cell lines.

Whereas in normal human thyroid tissue total cell mass is maintained by a balance between cell proliferation and apoptosis, the programmed cell death, in thyroid tumors this equilibrium is disrupted. In tumor cells, an augmented proliferation rate is no longer counterbalanced by an equally enhanced apoptosis resulting in an increased netto growth rate. To investigate regulation of apoptosis in thyroid tumors, we analyzed 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 in adenomas, whereas follicular carcinomas showed various expression of bcl-2 with decreased levels in 32% of cases. BclxL expression was comparable in all tissues examined. The pro-apoptotic protein bax was expressed at lower levels in carcinomas than in adenomas, whereas bak and bclx were expressed in the same order of magnitude in all tissues examined. In contrast, thyroid carcinoma cell lines exhibited a relatively strong expression of bclxL, but a weak expression of bcl-2. In all four cell lines, the amounts of the pro-apoptotic proteins bax, bak and bclx were higher than in most tumor tissues. Our data show that in thyroid tumors expression of members of the bcl-2 protein family is not uniform. Rather, the expression pattern of pro- and anti-apoptotic 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 tumor-igenesis.