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KMID : 0616619970030020547
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Journal of Soonchunhyang Medical College
1997 Volume.3 No. 2 p.547 ~ p.558
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Insulin-like growth factor and the IGF-I receptor inhibit etoposide-induced apoptosis
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Abstract
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The interaction of insulin-like growth factors(IGF) with the IGF-I receptor promotes cell proliferation and survival. The activation of the IGF-I receptor by its ligands IGF-I, IGF-II, and insulin plays critical role in growth and development. The specific role of the IGF-I receptor in development has been recently revealed that targeted disruption of the IGF-I receptor gene resulted in profound fetal growth retardation. Most cell types require IGF-I for growth in culture. In addition to its role in cell cycle progression, IGF-I appears to play an important role in cell survival. The specific mechanism by which IGF-1 promotes cell survival has not been clarified. IGF-I may directly prevent apoptosis. However, IGF-I could also promote cell culture survival by survival inducing the prokiferation of viable cells within a damaged cell population.
When exposed to the etoposide, R+ cells that constitutively overexpressed the IGF-IR arrested in S phase and subsequently underwent apoptosis as determined by the appearance of the pre-G1 apoptotic peak when studied by the flowcytometry and the charateristic internucleosomal fragmentation of DNA. The addition of IGF-I markly inhibited etoposide-induced apoptosis in a concentration-dependant manner. IGF-I was less effective in preventing apoptosis in parental R-and TC4 cells. These results demonstrate an important role for the IGF-I receptor as an inhibitor of apoptosis, independent of its mitogenic actions. These findings establish the relationship between IGF-IR levels and the extents of apoptosis. The TC4 cells expressing the truncated IGF-I receptor with a 108-amino-acid C-terminal truncation exhibited a dramatically impared ability to prevent the apoptosis, indicating that truncated IGF-I receptor lose the ability to prevent the apoptosis at the intramolecular level.
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