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Home | The Scope | What's New | Grand Rounds | Research In Progress RESEARCH IN PROGRESS PRESENTATION "The Role of IGFBP-3 in human disease" December 12, 2005
IGFBP-3 plays an important role in the growth and differentiation of many types of cells. The clinical significance of serum or cellular IGFBP-3 levels, polymorphisms in the igfbp-3 promoter, and post-translational modification of IGFBP-3 has been well appreciated: 1) the serum IGFBP-3 is a well-established aid to the diagnosis and monitoring of growth disorders; 2) IGFBP-3 is an important regulator of IGF actions in diseases such as cancer, diabetes and malnutrition; 3) IGFBP-3 expression is suppressed in many cancers; 4) the IGFBP-3 polymorphisms showed correlation to plasma IGFBP-3 levels and with advanced disease status in a certain cancer; and 5) IGFBP-3 is functionally changed in many different physiological conditions. This multifunctional IGFBP-3 achieves its biological effects through the well-known regulation of IGF/IGF-receptor interactions as well as via the recently discovered IGF-independent means (actions not involving IGF/IGF-receptor interactions). To date, several mechanisms have been proposed for the IGF-independent actions of IGFBP-3. IGFBP-3 may exert its actions on target cells by either activating cell surface receptors or by direct importation and translocation to the nucleus where it can induce its effect directly on gene expression. Recently we have demonstrated that IGFBP-3 inhibits cell growth in an IGF-independent manner by induction of apoptosis in a variety of cancer cells. We have further identified a membrane protein that specifically binds to IGFBP-3. Subsequent functional studies indicate that this membrane protein may be a functional IGFBP-3 receptor (IGFBP-3R). Overexpression of IGFBP-3R has led to a significant increase in binding of IGFBP-3 to the cell surface, and has potentiated IGFBP-3-induced apoptosis. In the prostate, the expression of IGFBP-3 and IGFBP-3R were suppressed during the progression of tumorigenesis, and the restoration of the IGFBP-3/IGFBP-3R axis resulted in significant in vitro and in vivo growth inhibition in prostate tumors, suggesting that t he IGFBP-3/IGFBP-3R axis represents an authentic growth inhibitory signaling cascade, which is impaired in prostate cancer cells. Taken together, there is ample evidence to support the concept that IGFBP-3 has unique intrinsic biological activities beyond its ability to interact with the IGF-IGFR axis and play a critical role in the pathogenesis of human diseases. For a printable version of this Research in Progress presentation, click here. For more information visit the Oncogenomics and Proteomics Research web page or contact Dr. Jogie-Brahim. For more information about VCU Pathology
Research in Progress presentations contact Updated December 14, 2005 |
