title: Expression of SMAD proteins, TGF-beta/activin signaling mediators, in human thyroid tissues.
abstract: OBJECTIVE
  To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-beta/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-beta and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-beta and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins.
  
  
  METHODS
  The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry.
  
  
  RESULTS
  The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions.
  
  
  CONCLUSIONS
  The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-beta/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.
authors.affiliation: Departamento de Biologia Celular e do Desenvolvimento, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Sílvia E
authors.initials: SE
authors.lastname: Matsuo
authors.forename: Ana Paula Z P
authors.initials: AP
authors.lastname: Fiore
authors.forename: Simone M
authors.initials: SM
authors.lastname: Siguematu
authors.forename: Kátia N
authors.initials: KN
authors.lastname: Ebina
authors.forename: Celso U M
authors.initials: CU
authors.lastname: Friguglietti
authors.forename: Maria C
authors.initials: MC
authors.lastname: Ferro
authors.forename: Marco A V
authors.initials: MA
authors.lastname: Kulcsar
authors.forename: Edna T
authors.initials: ET
authors.lastname: Kimura
mesh_terms: D028341:Activins / Q000502:physiology*; D000236:Adenoma / Q000378:metabolism; D018265:Carcinoma, Papillary, Follicular / Q000378:metabolism; D006044:Goiter, Nodular / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction / Q000502:physiology; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism*; D051899:Smad2 Protein / Q000032:analysis; D051900:Smad3 Protein / Q000032:analysis; D051901:Smad4 Protein / Q000032:analysis; D051906:Smad7 Protein / Q000032:analysis; D013964:Thyroid Neoplasms / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; C497806:SMAD7 protein, human; D051896:Smad Proteins, Receptor-Regulated; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D028341:Activins