Untersuchung zur IGF-I-vermittelten Signaltransduktion in der humanen Karzinoidzellinie LCC-18

This study investigates the IGF-I-mediated growth regulation of the cell line LCC-18, which was established from a human colon carcinoid tumour and has shown stable neuroendocrine properties for over 100 passages. Physiologically IGF-I is important for growth regulation and acts anti-apoptotic. Many tumour entities depend on IGF-I. In this assay the expression of IGF-I-receptors, the production and effects of IGF-I, and possible ways of signal transduction were investigated. RT-PCR showed Expression of IGF-I-receptors in LCC-18 cells. The production of IGF-I was evinced by RT-PCR, RIA and growth assays with conditioned cell media with and without Anti-IGF-I-antibodies. Growth assays with IGF-I revealed a concentration dependent, significant enhancement of cell proliferation. Growth assays with additional PD 098059 and Western blot analysis showed that MEK/MAPK plays an important role in the tranductional pathway. Also PI3 seems to be important for the pathway, as growth assays with IGF-I and LY 294002 show. Like in a variety of different tumours IGF-I is shown to be important for survival and proliferation of LCC-18 cells. Transient transfections with a chicken-IGF-I-promotor/Luciferase plasmid and subsequent stimulation with IGF-I suggest a positive feedback mechanism. The results of this study may be considered suitable to help to establish a new, alternative therapeutic approach for carcinoid and other tumours.