Role of IRS-1 Phosphorylation in IGF-1 and IL-4 Signaling in Breast Cancer
Abstract
Insulin-like growth factor-1 (IGF-1) stimulates proliferation of MCF-7 cells via the type I IGF receptor (IGF IR) and causes phosphorylation of the adaptor protein, insulin receptor substrate-1 (IRS-1). Interleukin 4 (IL-4) inhibits breast cancer cells and also phosphorylates IRS-1. The hypothesis was that IGF-1 and IL-4 phosphorylate different residues with IGF-1 treatment targeting IRS-1 for degradation via the proteasome. The goal of this project was to identify amino acids of IRS-1 phosphorylated by IGF-1 compared to IL-4 using two-dimensional electrophoresis (2DE) of phosphorylated IRS-1. However, as reported in the two previous reports, several technical difficulties and limitations of 2DE were encountered and impeded the completion of the tasks. In the final year, work was continued on 2DE of IRS-1 but despite sustained efforts, it has not been possible to detect IRS-1 after 2DE. Unfortunately, it appears that the large size, abundance in cells, and perhaps charge of IRS-1 may make it difficult to use this technique. As the long-term objective of my training was to identify new targets for breast cancer therapy and inhibit IGF action, I have successfully worked on two other projects - one to inhibit IGF-1 action in breast cancer cells using a humanized single chain antibody against IGF 1 R and a second project to inhibit metastasis of cancer cells using a truncated IGFIR that I have shown behaves in a dominant negative manner.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA418308
Entities
People
- Deepali Sachdev
Organizations
- University of Minnesota