Profiling the Roles of Insulin Receptor Substrate Isoforms 1 and 2 in Breast Cancer
Abstract
The insulin-like growth factor (IGF) system has been shown to play a role in breast cancer tumorigenesis and metastasis. Following IGF ligand stimulation, insulin receptor substrate (IRS) adaptor proteins are recruited to the IGF-1 receptor (IGF-1R) to mitigate downstream biochemical signaling namely via the MAPK and PI3K pathways. Data from our lab suggest that different isoforms (IRS-1 and IRS-2) exhibit a selective propensity for one of these signaling pathways to drive cellular behavior, where IRS-1 drives proliferation through Grb2/MAPK activation and IRS-2 stimulates motility through PI3K/Akt induction. Our early findings from this study now suggest overlapping and distinct sets of genes are driven by IRS-1 and IRS-2 following IGF-1 exposure. While both isoforms regulate expression at early (4H) and late (24H) time points, early IRS-2 genes are linked to adhesion and motility and late IRS-1 genes are important for cell cycle progression and proliferation. We are currently in the process of validating these global gene expression targets and signatures in order to better study the significance and potential clinical link to patient breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA508210
Entities
People
- Marc A. Becker
Organizations
- University of Minnesota