Role of IRS-1 Phosphorylation in IGF-1 and IL-4 Signaling in Breast Cancer
Abstract
Insulin-like growth factor 1 (IGF-I) stimulates proliferation of MCF-7 cells via the type I IGF( receptor (IGF 1 R) and causes phosphorylation of the adaptor protein, insulin receptor substrate-i (IRS- 1). interleukin 4 (IL-4) inhibits breast cancer cells and also phosphorylates IRS-i. The hypothesis is that IGF-I and 1L4 phosphorylate different residues with IGF-I treatment targeting IRS-i for degradation via the proteasome. The goal of this project is to identify amino acids of IRS-1 phosphorylated by IGF-I compared to IL-4 using two dimensional electrophoresis (2DE) of phosphorylated IRS-i. Several technical difficulties and limitations of 2DE have been encountered and impeded the completion of the tasks, Unfortunately, it appears that the large size, abundance in cells, and perhaps charge of IRS-i may make it difficult to use this technique. Despite sustained efforts, it has not been possible to detect IRS-i after 2DE. As the long-term objective of my training is to identify% new targets for breast cancer therapy, I have also worked on another project to inhibit IGF-I action in breast cancer cells using a humanized single chain antibody against IGF1R. In the coming year, work will be continued on 2DE of IRS-i along with an alternate approach of mutating residues in the putative destruction box motif of IRS-i in an attempt to inhibit the mitogenic effects of IGF-1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407504
Entities
People
- Deepali Sachdev
Organizations
- University of Minnesota