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Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines

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Abstract

Smad proteins have been shown to mediate the signal transduction pathway downstream of the transforming growth factor β (TGFβ). TGFβ 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 TGFβ-sensitivity, caused by inactivation of components of TGFβ 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 TGFβ 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 TGFβ response by Smad7 overexpression may be a mechanism for the tumor aggressiveness observed in undifferentiated thyroid tumors.

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Authors and Affiliations

  1. Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, SP, Brazil

    J. M. Cerutti & R. M. B. Maciel

  2. Department of Histology and Embryology, Institute of Biomedical Sciences, Universidade de São Paulo, Av Prof Lineu Prestes 1524, 05508-900, São Paulo, SP, Brazil

    K. N. Ebina, S. E. Matsuo, L. Martins &  E. T. Kimura

Authors
  1. J. M. Cerutti
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  2. K. N. Ebina
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  3. S. E. Matsuo
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  4. L. Martins
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  5. R. M. B. Maciel
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  6. E. T. Kimura
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Correspondence to E. T. Kimura.

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Cerutti, J.M., Ebina, K.N., Matsuo, S.E. et al. Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines. J Endocrinol Invest 26, 516–521 (2003). https://doi.org/10.1007/BF03345213

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