TNF-ALPHA-INDUCED ANTIPROLIFERATION IS NOT DEPENDENT ON THE AUTOCRINEACTION OF TGF-BETA-1 IN A THYROID-CANCER

The autocrine inhibitory action of transforming growth factor-beta 1 ( TGF-beta 1) may play an important role in maintaining the normal state of thyroid follicular epithelial cells. Deficiency of this regulatory mechanism has been implicated in the pathogenesis of nontoxic nodular goiter and thyroid epithelial cell cancer. Tumor necrosis factor-alph a (TNF-alpha) has an antiproliferative action in a human papillary thy roid carcinoma cell line, NP-PTC cells, through a receptor-mediated me chanism. In the present work, we studied the antiproliferative action of TNF-alpha. and TGF-beta 1 in NP-PTC cells. TNF-alpha induced TGF-be ta 1 mRNA and secretion of the latent form of TGF-beta 1. Both TNF-alp ha and TGF-beta 1 inhibited the proliferation of NP-PTC cells. A neutr alizing antibody specific to human TGF-beta 1 blocked the antiprolifer ative action of TGF-beta 1 on NP-PTC cells, but it failed to block TNF -alpha-induced antiproliferation. Further, TNF-alpha and TGF-beta 1 ac ted synergistically to inhibit NP-PTC cell proliferation. The results show that both TNF-alpha and TGF-beta 1 inhibit the proliferation of N P-PTC cells. However, the actions of TGF-beta 1 and TNF-alpha differ i n NP-PTC cells; TNF-alpha activates nuclear factor kappa B (NF-kappa B ) and TGF-beta 1 does not. Although TNF-alpha induced TGF-beta 1 mRNA and secretion of the latent form of TGF-beta 1, the antiproliferative action of TNF-alpha is not dependent on the autocrine action of TGF-be ta 1 in NP-PTC cells.