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

Sílvia Emiko Matsuo

Sílvia Emiko Matsuo Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes 1524, 05508-000 São Paulo, SP, Brazil

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Suzana Garcia Leoni

Suzana Garcia Leoni Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes 1524, 05508-000 São Paulo, SP, Brazil

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Alison Colquhoun

Alison Colquhoun Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes 1524, 05508-000 São Paulo, SP, Brazil

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Edna Teruko Kimura

Edna Teruko Kimura Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes 1524, 05508-000 São Paulo, SP, Brazil

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Transforming growth factor-beta 1 (TGF-β1) and activin A (ActA) induce similar intracellular signaling mediated by the mothers against decapentaplegic homolog (SMAD) proteins. TGF-β1 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-β1. Due to the concomitant expression of TGF-β1 and ActA in thyroid tumors, we investigated the effects of either TGF-β1 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-β1 and ActA knockdown cells. Recombinant TGF-β1 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-β1 and ActA generate SMADs signaling with each regulating the expression of their target genes, SMAD7 and c-MYC. Furthermore, TGF-β1 and ActA have an antiproliferative effect on thyroid papillary carcinoma cell, exerting an important role in the control of thyroid tumorigenesis.