The IGF axis and programmed cell death
Open Access
- 1 June 1999
- journal article
- review article
- Published by Wiley in Immunology & Cell Biology
- Vol. 77 (3) , 256-262
- https://doi.org/10.1046/j.1440-1711.1999.00822.x
Abstract
Insulin-like growth factors (IGF) are mitogenic peptides that have been implicated as positive regulators of cellular proliferation. In recent years, several studies have suggested an additional role for the IGF axis in the regulation of apoptosis. Signalling through the IGF receptor has been shown to have a potent survival function and protect cells from a variety of apoptotic stimuli. The actions of IGF are regulated by a family of high-affinity IGF binding proteins (IGFBP), which sequester the IGF from the IGF receptor. However, there is some evidence that one of these binding proteins, IGFBP-3, may have its own pro-apoptotic effects that are independent of its ability to modulate IGF bioavailability. In addition, it has been suggested that the tumour suppressor p53, a crucial mediator of apoptosis in response to cellular stress, may elicit several of its apoptotic effects through manipulation of components of the IGF axis. This review summarizes what is currently known about the role of the IGF system in the regulation of apoptosis, highlighting its implications in the context of tumorigenesis.Keywords
This publication has 72 references indexed in Scilit:
- Insulin/IGF-I Rescues Immortalized Brown Adipocytes from Apoptosis Down-Regulating Bcl-xS Expression, in a PI 3-Kinase- and Map Kinase-Dependent MannerExperimental Cell Research, 1998
- Development of Resistance to Insulin-like Growth Factor Binding Protein-3 in Transfected T47D Breast Cancer CellsBiochemical and Biophysical Research Communications, 1998
- Insulin-like Growth Factor Binding Protein-3 Induces Apoptosis in MCF7 Breast Cancer CellsBiochemical and Biophysical Research Communications, 1997
- Insulin-like Growth Factor 1 Inhibits Apoptosis Using the Phosphatidylinositol 3′-Kinase and Mitogen-activated Protein Kinase PathwaysJournal of Biological Chemistry, 1997
- Molecular Ordering of the Cell Death Pathway: Bcl-2 AND Bcl-xL FUNCTION UPSTREAM OF THE CED-3-LIKE APOPTOTIC PROTEASESPublished by Elsevier ,1996
- Estradiol and Antiestrogens Regulate a Growth Inhibitory Insulin-like Growth Factor Binding Protein 3 Autocrine Loop in Human Breast Cancer CellsJournal of Biological Chemistry, 1996
- Induction of the growth inhibitor IGF-binding protein 3 by p53Nature, 1995
- A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesisNature, 1994
- Insulin-like growth factor-I (IGF-I) and transforming growth factor- beta 1 release IGF-binding protein-3 from human fibroblasts by different mechanismsEndocrinology, 1992
- Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6)Progress in Growth Factor Research, 1991