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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Philipps-Universität Marburg
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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This item has been published with the following license: In Copyright