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Project B

Project B

 

 

Name:

Prof. Dr. Georg Brabant

 

Institution:

Department of Clinical Endocrinology

 

Telephone:

0049-511-532-6528

 

Email:

Brabant.Georgmh-hannover.de

 

Research focus:

Adhesion of epithelial cells is mediated by a specific complex, the adherens junction. Adherens junctions are composed of the transmembranous protein E-Cadherin, which interacts with E-Cadherins of adjacent cells. Catenins bind to the intracellular domain of E-Cadherin and connect the complex with the cytoskeleton. Cell-cell adhesion is essential for tissue organization during development and for maintenance of tissue integrity in adult organisms [1].

 

A signaling function of ß-Catenin was discovered in recent years. ß-Catenin that is outside the adherens junctions is rapidly degraded. Signaling via the Wnt pathway induced by binding of the wnt ligand to cell membrane receptors inhibits ß-Catenin degradation. ß-Catenin accumulates, translocates to the nucleus and binds to transcription factors of the TCF/LEF family. This bipartite complex activates transcription of a series of genes, including c-myc, fra-1, cyclin D1 [2, 3].

 

Projects:

Our group analyzes the role of cell-cell adhesion proteins in the progression of thyroid cancer. As in many epithelial carcinoma a loss of E-Cadherin expression is observed in thyroid carcinomas which correlates with an increased invasiveness and metastasis [3]. This loss of E-cadherin expression is due to hypermethylation of the promoter. We are now applying E-cadherin reexpression treatments to search for redifferentiation strategies for thyroid carcinoma.

 

Situations favouring the accumulation of monomeric ß-Catenin in the nucleus have been linked to tumorigenesis in a series of cell types. Most commonly known are mutations of the APC gene that are initially involved in colon carcinogensis. Our group investigates expression and function of elements of the Wnt pathway in thyroid cells are. Future projects concern the pathophysiological relevance of the Wnt pathway in thyroid carcinogenesis by mutational analysis and expression analysis.

 

The project is granted by the Deutsche Krebshilfe.

 

Group members:

Prof. Dr. Georg Brabant

Dr. Karen Helmbrecht, Postdoctoral Scientist

Julia Resch, Technician

Natalja Kremenevskaja, Doctoral Thesis Worker

Sibylle Schomburg, Doctoral Thesis Worker

 

Methods:

Cell Culture, Transfection, Western Blot, Immunohistochemistry, Northern Blot, in situ-Hybridization, Sequencing, PCR, Cloning

 

Key References:

  1. Pötter E, Bergwitz C, Brabant G. The cadherin-catenin system: implications for growth and differentiation of endocrine tissues. Endocr Rev 1999;20:207-39.

  2. Polakis P. Wnt signaling and cancer. Genes Dev. 2000;14:1837-51.

  3. Taipale J, Beachy PA. The Hedgehog and Wnt signalling pathways in cancer. Nature 2001;411:349-354. 4. von Wasielewski R, Rhein A, Werner M. Immunohistochemical detection of E-cadherin in differentiated thyroid carcinomas correlates with clinical outcome. Cancer Res 1997;57:2501-7.

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