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Insulin-Like Growth Factor Binding Protein-1 Interacts with Integrins to Inhibit Insulin-Like Growth Factor-Induced Breast Cancer Growth and Migration

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Annual summary rept. 1 Jul 2002-30 Jun 2003

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The insulin-like growth factor IGF system and extracellular matrix proteins are key regulators of the malignant breast cancer phenotype. Both IGFs and extracellular matrix proteins communicate wit epithelial cells by ligating cell surface receptors. Therefore, ligand-receptor interactions of the two systems are relevant treatment targets in breast cancer cell growth. Studies have shown that IGFBP-l can bind to IGF and prevent IGF from interacting with its receptor and inhibit breast cancer cell growth. IGFBP-1 has also been shown to interact with extracellular matrix protein receptors, integrins, on the cell surface through an Arg-Cly-Asp RGD integrin recognition sequence. This proposal will test the hypothesis that IGFBP-1 interrupts ligand-receptor interactions between extracellular matrix proteins and integrins. The key research accomplishment is the conclusion that expression of a mutant form of IGFBP-l that cannot bind integrins at reasonable levels is not technically achievable using the Pichia pastoris yeast expression system. An alternative approach will be used to express mutant IGFBP-1. The successful expression and purification of mutant IGFBP-1 protein is needed to test whether IGFBP-1 can be used as a strategy to neutralize integrin function in an RGD-dependent manner.

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  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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