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  • Original Paper
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Gene expression analysis reveals evidence for inactivation of the TGF-β signaling cascade in autonomously functioning thyroid nodules

Oncogene volume 23, pages 795–804 (2004)Cite this article

Abstract

Molecular eventsthat lead to the development of autonomously functioning thyroid nodules (AFTNs) are somatic mutations of the thyrotropin receptor (TSHR) in approximately 60% of the nodules and less frequently, somatic mutations in the Gsα protein. However, AFTNs without known mutations indicate that other causes remain to be identified. Moreover, the impact of constitutively activating TSHR mutations on the signal transduction network of the thyroid epithelial cell is unknown. We therefore investigated gene expression in 15 AFTNs and their surrounding tissue using Affymetrix GeneChips. Most prominently, data analysis revealed a changed pattern of gene expression in the TGF-β signaling cascade and 25 differentially regulated genes in AFTNs, including thyroid peroxidase, type I iodothyronine deiodinase and sialyltransferase (SIAT) 1. Strikingly coexpression of SIAT 1 and TSHR in COS-7 cells increased TSH binding and cell surface expression of the TSHR. Moreover, differences in gene expression patterns for AFTNs with and without TSHR mutations indicate specific alterations of signal transduction in AFTNs without TSHR mutations. These results suggest that AFTNs with TSHR mutations harbor further mechanisms of forward stimulation. Furthermore, they give important leads to elucidate the molecular etiology of AFTNs without TSHR mutations.

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Acknowledgements

We are grateful to Gudrun Bethge, Eileen Bösenberg and Petra Süptitz for their excellent technical assistance. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG/Pa423/10-1) and the BMBF Interdisciplinary Center for Clinical Research at the University of Leipzig (01KS9504, Projects B20 and B14, Z16-CHIP2). The microarray analysis was conducted at the IZKF Leipzig core facility. KK is supported by IZKF Leipzig, BMBF Interdisciplinary Center for Clinical Research at the University of Leipzig 9504 (01KS 9504, project Z3).

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Authors and Affiliations

  1. III. Medical Department, University of Leipzig, Ph.-Rosenthal-Str. 27, Leipzig, D-04103, Germany

    Markus Eszlinger, Knut Krohn, Romy Frenzel, Anke Tönjes & Ralf Paschke

  2. Interdisciplinary Center for Clinical Research Leipzig, Johannisallee, Leipzig, 30a 04103, Germany

    Knut Krohn

  3. Institute of Biometrics and Medical Informatics, University of Magdeburg, Leipziger Str. 44, Magdeburg, 39120, Germany

    Siegfried Kropf

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  1. Markus Eszlinger
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Correspondence to Ralf Paschke.

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Eszlinger, M., Krohn, K., Frenzel, R. et al. Gene expression analysis reveals evidence for inactivation of the TGF-β signaling cascade in autonomously functioning thyroid nodules. Oncogene 23, 795–804 (2004). https://doi.org/10.1038/sj.onc.1207186

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