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Research Paper
Insulin-like Growth Factor Binding Protein-2 Stimulates Proliferation and Activates Multiple Cascades of the Mitogen-Activated Protein Kinase Pathways in NIH-OVCAR3 Human Epithelial Ovarian Cancer Cells
Shilla Chakrabarty and Laura Kondratick
volume 5 | issue 2
february 2006Pages: 189-197
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Insulin-like growth factor binding protein-2 (IGFBP-2), the second most abundant IGFBP in the circulation, is dramatically increased in the serum and ovarian cyst fluid of women with epithelial ovarian cancer. The specific role of IGFBP-2 in ovarian carcinogenesis remains elusive. Using NIH-OVCAR3 human epithelial ovarian cancer cells, we have evaluated the effects of IGFBP-2 and its antibody on cell proliferation, activation of mitogen-activated protein kinase (MAP kinase) pathways, and on cytokine expression. Treatment of the cells with IGFBP-2 stimulates cell growth significantly (P < .05) and potentiates the activation of (a) the extracellular signal regulated kinases (ERK1/2) signaling pathway, which transduces cell-specific growth and differentiation signals; (b) the stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK) pathway, which is activated by environmental stresses, inflammatory cytokines, growth factors, and G-protein coupled receptor (GPCR) agonists; and (c) the p38 MAP kinase pathway, which mediates inflammatory and stress responses. Suppression of IGFBP-2, with its neutralizing antibody, significantly (P < .05) retards cell growth, blocks the activation of all three cascades of the MAPK pathways, and downregulates the expression of a number of potential cancer-promoting cytokines. These novel findings may have important clinical implications for developing innovative strategies for the treatment and management of ovarian cancer.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.