Phosphorylation of Intracellular IGF Binding Protein-3 by the IGF Signaling Cascade is Essential for Its Growth-Enhancing in Mammary Epithelial
Final rept. 1 Jul 2001-30 Jun 2004
RUTGERS - THE STATE UNIV PISCATAWAY NJ
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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 IGF-I to activate chemical signals within the cell that lead to gene activation is enhanced in cells expressing IGFBP-3. In addition, IGFBP-3 within breast cancer cells exists in a phosphorylated form, with phosphorylation occurring on serine residues. This is the first report that intracellular IGFBP-3 is phosphorylated. Preliminary studies indicate that treatment with IGF-I results in a decrease in IGFBP-3 phosphorylation. This supports the 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.
- Medicine and Medical Research