Item type:Thesis, Open Access

Untersuchungen zur transkriptionellen Regulation des Chromogranin A Gens und seine Anwendung zum zellspezifischen therapeutischen Gentransfer in neuroendokrine Pankreastumorzellen

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Philipps-Universität Marburg

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Abstract

Difficulties in treatment of neuroendocrine tumors results in a poor survival rate. The regulated gene transfer offers new possibilities in the treatment of neuroendocrine tumors. As a basis for gene therapy the transcriptional regulation of the human chromogranin A gene, a member of the granin/secretogranin family of secretory peptides, was analysed. Sequence analysis of the chromogranin A gene showed a sequence homology in the proximal promoter region of the chromogranin A gene of the rat, mouse, cattle and human chromogranin A gene. All promoters showed putative transcription factor binding sites for Sp1, Egr-1, CRE and a TATA-box in the proximal promoter region. The CRE seemed to be essential for the neuroendocrine specific expression of human chromogranin A. Due to the CRE the human chromogranin A promoter activity was stimulated by cAMP and gastrin. Transient transfection studies showed that the sodiumiodidesymporter (NIS) could be functionally expressed in the neuroendocrine pancreatic tumor cell line BON-1 under control of the chromogranin A promotor. The regulated gene transfer of the NIS offers the possibility of a radioiodide therapy of neuroendocrine tumors on analogy of the treatment of thyroid cancer.

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Bert, Tillmann (128406534): Untersuchungen zur transkriptionellen Regulation des Chromogranin A Gens und seine Anwendung zum zellspezifischen therapeutischen Gentransfer in neuroendokrine Pankreastumorzellen. : Philipps-Universität Marburg 2003-09-24. DOI: https://doi.org/10.17192/z2003.0560.

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This item has been published with the following license: In Copyright