The IGF axis and programmed cell death

Insulin-like growth factors (IGF) are mitogenic peptides that have been imp licated as positive regulators of cellular proliferation. In recent years, several studies have suggested an additional role for the IGF axis in the r egulation of apoptosis. Signalling through the IGF receptor has been shown to have a potent survival function and protect cells from a variety of apop totic stimuli. The actions of IGF are regulated by a family of high-affinit y IGF binding proteins (IGFBP), which sequester the IGF from the IGF recept or. However, there is some evidence that one of these binding proteins, IGF BP-3, may have its own pro-apoptotic effects that are independent of its ab ility to modulate IGF bioavailability. In addition, it has been suggested t hat the tumour suppressor p53, a crucial mediator of apoptosis in response to cellular stress, may elicit several of its apoptotic effects through man ipulation of components of the IGF axis. This review summarizes what is cur rently known about the role of the IGF system in the regulation of apoptosi s, highlighting its implications in the context of tumorigenesis.