This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eszlinger, M. Articles by Paschke, R. Search for Related Content PubMed PubMed Citation Articles by Eszlinger, M. Articles by Paschke, R.

Complementary DNA Expression Array Analysis Suggests a Lower Expression of Signal Transduction Proteins and Receptors in Cold and Hot Thyroid Nodules

Third Medical Department, University of Leipzig, D-04103 Leipzig, Germany

Address all correspondence and requests for reprints to: R. Paschke, M.D., Third Medical Department, University of Leipzig, Ph. Rosenthal Strasse 27, D-04103 Leipzig, Germany. E-mail: pasr{at}server3.medizin.uni-leipzig.de

Abstract

Autonomously functioning thyroid nodules are characterized by an increased proliferation and function, which is predominantly caused by constitutively activating TSH receptor mutations leading to an activation of cAMP. In contrast to autonomously functioning thyroid nodules, cold thyroid nodules are functionally inactive and less differentiated. Their molecular cause is still unknown. To further investigate the pathophysiological aspects of autonomously functioning thyroid nodules and to elucidate the molecular etiology of cold thyroid nodules, it is essential to identify genes with differential expression in autonomously functioning thyroid nodules and cold thyroid nodules and to compare this expression to that in normal surrounding tissue. The list of possible candidates for differential regulation ranges from growth factors and their receptors to transcription factors or oncogenes. Therefore, we evaluated the potential of cDNA arrays and studied the expression of 588 known genes from 6 different classes of proteins in thyroid nodules characterized for their function. Forty-seven genes showed a differential expression between nodular and surrounding tissue identified by the expression arrays. The differential expression of 15 transcripts was verified by real-time PCR. About 25% of the transcripts determined by LightCycler PCR are considered false positives because data from PCR and array analysis did not agree. This indicates the reliability of cDNA expression arrays to identify differentially expressed genes in thyroid nodules compared with their surrounding tissue. The 15 selected genes were additionally quantified by real-time PCR in 7 additional cold thyroid nodules, autonomously functioning thyroid nodules, and their surrounding tissues. The highest number of differentially expressed genes was in the group of signal transduction proteins (4 of 38 detectable genes) and extracellular cell signaling and communication proteins (2 of 62 detectable genes). In contrast, transcripts of other classes of proteins were unchanged (e.g. DNA-binding molecules and stress responses). Most of the transcripts were down-regulated in autonomously functioning thyroid nodule and cold thyroid nodule compared with the respective surrounding tissue. This finding could be the result of a dominant activation of a signal transduction pathway, with the cAMP pathway being the likely candidate for autonomously functioning thyroid nodules. The qualitatively similar pattern of changes in this limited number of genes in autonomously functioning thyroid nodules and cold thyroid nodules could suggest a similar dominant activation of a specific signaling cascade in cold thyroid nodules as the constitutively activating mutations in autonomously functioning thyroid nodules.

This article has been cited by other articles:

				K. Krause, B. Jessnitzer, and D. Fuhrer Proteomics in Thyroid Tumor Research J. Clin. Endocrinol. Metab., August 1, 2009; 94(8): 2717 - 2724. [Abstract] [Full Text] [PDF]

				K. Fujarewicz, M. Jarzab, M. Eszlinger, K. Krohn, R. Paschke, M. Oczko-Wojciechowska, M. Wiench, A. Kukulska, B. Jarzab, and A. Swierniak A multi-gene approach to differentiate papillary thyroid carcinoma from benign lesions: gene selection using support vector machines with bootstrapping Endocr. Relat. Cancer, September 1, 2007; 14(3): 809 - 826. [Abstract] [Full Text] [PDF]

				M. Eszlinger, K. Krohn, A. Kukulska, B. Jarzab, and R. Paschke Perspectives and Limitations of Microarray-Based Gene Expression Profiling of Thyroid Tumors Endocr. Rev., May 1, 2007; 28(3): 322 - 338. [Abstract] [Full Text] [PDF]

				O. L. Griffith, A. Melck, S. J.M. Jones, and S. M. Wiseman Meta-Analysis and Meta-Review of Thyroid Cancer Gene Expression Profiling Studies Identifies Important Diagnostic Biomarkers J. Clin. Oncol., November 1, 2006; 24(31): 5043 - 5051. [Abstract] [Full Text] [PDF]

				A.-C. Gerard, M. Boucquey, M.-F. van den Hove, and I. M. Colin Expression of TPO and ThOXs in human thyrocytes is downregulated by IL-1{alpha}/IFN-{gamma}, an effect partially mediated by nitric oxide Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E242 - E253. [Abstract] [Full Text] [PDF]

				J. Maier, H. van Steeg, C. van Oostrom, S. Karger, R. Paschke, and K. Krohn Deoxyribonucleic Acid Damage and Spontaneous Mutagenesis in the Thyroid Gland of Rats and Mice Endocrinology, July 1, 2006; 147(7): 3391 - 3397. [Abstract] [Full Text] [PDF]

				K. Krohn, M. Eszlinger, R. Paschke, I. Roeder, and E. Schuster Increased power of microarray analysis by use of an algorithm based on a multivariate procedure Bioinformatics, September 1, 2005; 21(17): 3530 - 3534. [Abstract] [Full Text] [PDF]

				K. Krohn, D. Fuhrer, Y. Bayer, M. Eszlinger, V. Brauer, S. Neumann, and R. Paschke Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter Endocr. Rev., June 1, 2005; 26(4): 504 - 524. [Abstract] [Full Text] [PDF]

				B. Jarzab, M. Wiench, K. Fujarewicz, K. Simek, M. Jarzab, M. Oczko-Wojciechowska, J. Wloch, A. Czarniecka, E. Chmielik, D. Lange, et al. Gene Expression Profile of Papillary Thyroid Cancer: Sources of Variability and Diagnostic Implications Cancer Res., February 15, 2005; 65(4): 1587 - 1597. [Abstract] [Full Text] [PDF]

				M. Eszlinger, K. Krohn, K. Berger, J. Lauter, S. Kropf, M. Beck, D. Fuhrer, and R. Paschke Gene Expression Analysis Reveals Evidence for Increased Expression of Cell Cycle-Associated Genes and Gq-Protein-Protein Kinase C Signaling in Cold Thyroid Nodules J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1163 - 1170. [Abstract] [Full Text] [PDF]