Transforming growth factor-beta1 and activin A generate antiproliferative signaling in thyroid cancer cells.
Transforming growth factor-beta 1 (TGF-beta1) and activin A (ActA) induce similar intracellular signaling mediated by the mothers against decapentaplegic homolog (SMAD) proteins. TGF-beta1 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-beta1. Due to the concomitant expression of TGF-beta1 and ActA in thyroid tumors, we investigated the effects of either TGF-beta1 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-beta1 and ActA knockdown cells. Recombinant TGF-beta1 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-beta1 and ActA generate SMADs signaling with each regulating the expression of their target genes, SMAD7 and c-MYC. Furthermore, TGF-beta1 and ActA have an antiproliferative effect on thyroid papillary carcinoma cell, exerting an important role in the control of thyroid tumorigenesis.
Matsuo
Sílvia Emiko
SE
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.
Leoni
Suzana Garcia
SG
Colquhoun
Alison
A
Kimura
Edna Teruko
ET
D028341:Activins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016259:Genes, myc; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D034741:RNA, Small Interfering; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D051899:Smad2 Protein / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics; D051901:Smad4 Protein / Q000235:genetics; D051906:Smad7 Protein / Q000235:genetics; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D051785:Smad Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits