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The Scope | Grand Rounds | Research In Progress Schedule RIP Presentation | RIP Archive RESEARCH IN PROGRESS PRESENTATION "Dysregulation
of the IGFBP-3 / IGFBP-3R Axis in ProstateTumorigenesis" The insulin-like growth factors (IGFs) and their receptors and binding proteins (BPs) play essential roles in tumorigenesis and progression of a variety of cancers. IGFBP-3, a member of the IGFBP family and the most abundant binding protein in human serum, plays an important role in the growth regulation of cancer cells, independent of its role as amodulator of IGF-I bioactivity. In support of these observations, the involvement of IGFBP-3 in cell growth inhibition and induction of apoptosis in prostate cancer has been demonstrated, although the specific mechanisms involved are unclear. Recently we have 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). We have initiated a study of the role of IGFBP-3/ IGFBP-3R in the regulation of prostate tumorigenesis, using two distinct lineages of human SV40Tag-immortalized nonmalignant prostate epithelium cell lines: the P69SVT40 (P69) lineage [Bae et. al., Int. J. Cancer, 1994] and its tumorigenic and metastatic derivative M12, and the lineage of BPH-1 [Hayward et. al., In Vitro Cell Dev. Biol., 1995] with its tumorigenic derivative CAFTD-02. In both series, nontumorigenic prostate cell lines expressed both IGFBP-3 and IGFBP-3R, whereas their respective tumorigenic derivatives produced minimal levels of these proteins. These expression patterns of IGFBP-3 and IGFBP-3R are inversely related to the growth rate of the cells. The observed decreased expression in tumorigenic derivatives is consistent with our findings of down-regulation of the mRNA of IGFBP-3 and IGFBP-3R in prostate tumor tissues. Messenger RNA for both IGFBP-3 and IGFBP-3R was expressed in all of the normal prostate tissues tested by RT-PCR, whereas there was decreased expression of IGFBP-3 and/or IGFBP-3R in the prostate tumors. Collectively, these observations suggest that IGFBP-3 and IGFBP-3R may play an important role in prostate tumorigenesis, although the mechanism is still not clear. Studies in which the expression of IGFBP-3 and IGFBP-3R is modified, singly and in concert, are ongoing, and should further elucidate the role of these proteins in prostate cancer progression. For more information contact Lingbo Fan, MD at lfan@mail1.vcu.edu or visit the Oncogenomics and Proteomics Research Program web page. For more information about VCU Pathology
Research in Progress presentations contact Updated March 8, 2005 |
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