Perspectives in mammalian IGFBP-3 biology: local vs. systemic action.

摘要

Insulin-like growth factor (IGF) binding protein (IGFBP)-3 has traditionally been defined by its role as a binding protein and its association with IGF delivery and availability. Development of non-IGF binding IGFBP-3 analogs and the use of cell lines devoid of type 1 IGF receptors (IGF-R) have led to critical advances in the field of IGFBP-3 biology. These studies show that IGFBP-3 has IGF-independent roles in inhibiting cell proliferation in cancer cell lines. Nuclear transcription factor, retinoid X receptor (RXR)-alpha, and IGFBP-3 functionally interact to reduce prostate tumor growth and prostate-specific antigen in vivo. Moreover, IGFBP-3 inhibits insulin-stimulated glucose uptake into adipocytes independent of IGF. The purpose of this review is to highlight IGFBP-3 as a novel effector molecule and not just another "binding protein