Item type:Thesis, Open Access

Wirkung und Wirkungsweise von Insulin-like Growth-factor-I auf das proliferative Wachstum neuroendokriner Tumorzellen am Beispiel der humanen Karzinoidzelllinie BON

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Date

2004-11-03

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Philipps-Universität Marburg
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Abstract

Carcinoids are neuroendocrine tumours developed throughout the gastrointestinal tract. There is no effective curative therapeutic strategy apart from surgery. The expression of the IGF-I-receptor and IGF-I secretion had already been shown in this type of tumours. Both parts of the IGF-System are well documented to be very important for development and maintenance of a malignant phenotype. Recently, the IGF-System was suggestet to be a new and promising target for anticancer strategies. The aim of this study was to characterize the role of IGF-I and its signal transduction pathways in growth regulation of human carcinoid BON cells. The expression of the IGF-receptor had been shown by receptor binding studies. The secretion of IGF-I was messured by radioimmunoassay. Treatment of BON cells with IGF-I increases significantly cell proliferation. It had been found, that PD 98059, a specific inhibitor of ERK 1 and 2, and LY 294002, a specific inhibitor of PI3-kinase, are important for basal and IGF-I induced cell proliferation. Moreover, there is every indication that those two signalling cascades are linked. The effects on map-kinase was visualised by map-kinase assay. Finally it had been demonstrated by transfection of an IGF-I-promotor-plasmid, that both signal transducing pathways influence IGF-I gene expression. In connection with the presence of IGF-receptor-I and the proven IGF-I secretion, it might be concluded, that IGF-I act on BON cells in an autocrine way. Consequently, the IGF-I system may represent an attractive and new therapeutic target for the treatment of human endocrine GEP tumours. Several strategies seem possible: hitting (1) the IGF-I-receptor, (2) its signal transduction machinery or (3) the expression of IGF-I.

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Dates
Created: 2004Issued: 2004-11-03Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2004.0496
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
PI3-KinaseCarcinoidBON-ZellenBON-cellsNeuroendocrine tumourIGF-IIGF-I-RezeptorNeuroendokriner TumorSignal transduction
DFG-subjects
CarcinoidMAP-KinaseInsulin-like Growth Factor ISignaltransduktionInsulin-like Growth Factor
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2004.0496
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Pircher, Benedikt Johannes: Wirkung und Wirkungsweise von Insulin-like Growth-factor-I auf das proliferative Wachstum neuroendokriner Tumorzellen am Beispiel der humanen Karzinoidzelllinie BON. : Philipps-Universität Marburg 2004-11-03. DOI: https://doi.org/10.17192/z2004.0496.

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