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