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

Die Therapieoptionen zur Behandlung metastasierter neuroendokriner Tumore sind bisher ineffektiv. Der regulierte Gentransfer könnte eine weitere Möglichkeit eröffnen, metastasierte neuroendokrine Tumore zu behandeln. In der vorliegenden Arbeit wurde daher die transkriptionelle Regulation von Chr...

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Bibliographic Details
Main Author: Bert, Tillmann
Contributors: Simon, B. (PD Dr. med) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2003
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Table of Contents: 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.