TNF-alpha-induced antiproliferation is not dependent on the autocrine action of TGF-beta 1 in a thyroid cancer cell line.
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-alpha (TNF-alpha) has an antiproliferative action in a human papillary thyroid carcinoma cell line, NP-PTC cells, through a receptor-mediated mechanism. In the present work, we studied the antiproliferative action of TNF-alpha and TGF-beta 1 in NP-PTC cells. TNF-alpha induced TGF-beta 1 mRNA and secretion of the latent form of TGF-beta 1. Both TNF-alpha and TGF-beta 1 inhibited the proliferation of NP-PTC cells. A neutralizing antibody specific to human TGF-beta 1 blocked the antiproliferative 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 acted synergistically to inhibit NP-PTC cell proliferation. The results show that both TNF-alpha and TGF-beta 1 inhibit the proliferation of NP-PTC cells. However, the actions of TGF-beta 1 and TNF-alpha differ in 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-beta 1 in NP-PTC cells.
Pang
X P
XP
Research Laboratory, West Los Angeles Veterans Affairs Medical Center, CA.
Yoshimura
M
M
Wang
J
J
Dubinett
S M
SM
D000906:Antibodies / Q000494:pharmacology; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D016328:NF-kappa B; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha