Transforming growth factor-β1 and activin A generate anti proliferative signaling in thyroid cancer cells

被引:34
作者
Matsuo, Silvia Emiko [1 ]
Leoni, Suzana Garcia [1 ]
Colquhoun, Alison [1 ]
Kimura, Edna Teruko [1 ]
机构
[1] Univ Sao Paulo, Dept Cell & Dev Biol, Inst Biomed Sci, BR-05508000 Sao Paulo, Brazil
关键词
D O I
10.1677/joe.1.06713
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Transforming growth factor-beta 1 (TGF-beta 1) and activin A (ActA) induce similar intracellular signaling mediated by the mothers against decapentaplegic homolog (SMAD) proteins. TGF-beta 1 is a potent antimitogenic factor for thyroid follicular cells, while the role of ActA is not clear. In our study, the proliferation of TPC-1, the papillary thyroid carcinoma cell line, was reduced by both recombinant ActA and TGF-beta 1. Due to the concomitant expression of TGF-beta 1 and ActA in thyroid tumors, we investigated the effects of either TGF-beta 1 or ActA gene silencing by RNA interference in TPC-1 cells in order to distinguish the specific participation of each in proliferation and intracellular signaling. An increased proliferation and reduced SMAD2, SMAD3, and SMAD4 mRNA expression were observed in both TGF-beta 1 and ActA knockdown cells. Recombinant TGF-beta 1 and ActA increased the expression of inhibitory SMAD7, whereas they reduced c-MYC. Accordingly, we detected a reduction in SMAD7 expression in knockdown cells while, unexpectedly, c-MYC was reduced. Our data indicate that both TGF-beta 1 and ActA generate SMADs signaling with each regulating the expression of their target genes, SMAD7 and c-MYC. Furthermore, TGF-beta 1 and ActA have an antiproliterative effect on thyroid papillary carcinoma cell, exerting an important role in the control of thyroid tumorigenesis.
引用
收藏
页码:141 / 150
页数:10
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