Phosphorylation of Intracellular IGF Binding Protein-3 by the IGF signaling Cascade is Essential for its Growth-Enhancing Effect in Mammary Epithelial Cells

摘要

The insulin-like growth factors (IGF) are involved in processes leading to tumorigenesis and metastasis. The IGFs stimulate growth of mammary epithelial cells, the site of origin of ductal breast carcinomas. Their ability to stimulate growth is modulated by IGF binding protein-3. The goal of these studies is to determine how IGFBP-3 enhances IGF action. Two established cell lines genetically engineered to express IGFBP-3 serve as the experimental models. We have found that the ability of IGFBP-3 enhances IGF-I stimulated cell cycle progression in these cells and if IGF-I phosphorylates IGFBP-3. Establishing whether or not the IGF signaling cascade results in phosphorylation of IGFBP-3 is central to the overall hypothesis that intracellular IGFBP-3 plays a role in IGF-I stimulation of cell cycle progression. Further work in this area using breast tumor specimens will determine whether this pathway is disrupted in breast cancer. Potential therapies for breast cancer may include treatments that alter phosphorylation or dephoshorylation of the IGFBP-3 protein.