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Identification of a Wnt/ß-Catenin Signaling Pathway in Human Thyroid Cells

Departments of Clinical Endocrinology (K.H., G.B.), Molecular Biology (A.K.), and Pathology (R.v.W.), Medizinische Hochschule Hannover, D-30625 Hannover, Germany

Address all correspondence and requests for reprints to: Dr. G. Brabant, Medizinische Hochschule Hannover, Klinische Endokrinologie, Carl Neuberg Strasse 1, D-30625 Hannover, Germany. E-mail: brabant.georg{at}mh-hannover.de

ß-Catenin is a structural component of the adherens junctions. Outside the adherens junctions a complex consisting of glycogen synthase kinase 3ß, the tumor suppressor adenomatous polyposis coli, and axin constantly targets ß-Catenin for degradation to keep levels of free ß-Catenin low. Free ß-Catenin is able to bind to transcription factors of the T cell factor/lymphoid-enhancing factor family and to stimulate transcription of target genes. This signaling function of ß-Catenin is activated by extracellular Wnt factors that bind to Frizzled receptors and induce inhibition of ß-Catenin degradation.

By RT-PCR and subcloning, we observed the expression of five Wnt factors, three members of the Frizzled receptor family, and all known Disheveled isoforms in thyroid cells. Immunoprecipitation studies demonstrated the formation of the complex targeting ß-Catenin for degradation. Introduction of a degradation resistant ß-Catenin into the thyroid carcinoma cell line WRO induced appearance of monomeric ß-Catenin as shown by size fractionation and nuclear ß-Catenin immunostaining. Reporter gene assays demonstrated a stimulation of T cell factor/lymphoid-enhancing factor-mediated transcription in these cells. In ARO cells, a thyroid carcinoma cell line carrying a mutated adenomatous polyposis coli gene, monomeric ß-Catenin and nuclear immunostaining were observed. In summary, our data indicate that elements of the Wnt signaling pathway are expressed in thyroid cells and that this pathway is functionally active.

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