Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines.
Smad proteins have been shown tomediate the signal transduction pathway downstream of the transforming growth factor beta (TGFbeta). TGFbeta induces the phosphorylation of Smad2 and Smad3 which associate with Smad4 and translocate to the nucleus where they regulate gene transcription; besides these stimulatory Smads, the inhibitory Smads, Smad6 and Smad7, oppose signaling by blocking receptors and interrupting the phosphorylation of Smads2/3. The loss of TGFbeta-sensitivity, caused by inactivation of components of TGFbeta signaling, as Smad4, underlies a wide variety of human disorders, including cancer. In addition, the overexpression of the inhibitory Smad7, which prevents the phosphorylation of Smad2/3 and consequently inhibits TGFbeta signaling pathways, was observed in some diseases. In the present study we investigated the expression of Smad4 and Smad7 in thyroid cell lines (NPA papillary carcinoma, WRO follicular carcinoma and ARO anaplastic carcinoma) by RT-PCR and immunocytochemistry. Our results show that Smad4 was expressed in all thyroid cell lines and controls analyzed, differently from other classes of tumors where Smad4 expression was deleted. On the other hand, Smad7 was overexpressed in ARO anaplastic cell line, the most malignant follicular thyroid carcinoma. Our data suggest that the abrogation of the TGFbeta response by Smad7 overexpression may be a mechanism for the tumor aggressiveness observed in undifferentiated thyroid tumors.
Cerutti
J M
JM
Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Ebina
K N
KN
Matsuo
S E
SE
Martins
L
L
Maciel
R M B
RM
Kimura
E T
ET
D018263:Adenocarcinoma, Follicular / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D010750:Phosphoproteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051901:Smad4 Protein; D051902:Smad5 Protein; D013964:Thyroid Neoplasms / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C497796:SMAD4 protein, human; C497797:SMAD5 protein, human; D051901:Smad4 Protein; D051902:Smad5 Protein; D015534:Trans-Activators