Profiling the Roles of Insulin Receptor Substrate Isoforms 1 and 2 in Breast Cancer
Annual summary rept. 1 Apr 2008-31 Mar 2009
MINNESOTA UNIV MINNEAPOLIS
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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 Grb2MAPK activation and IRS-2 stimulates motility through PI3KAkt 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.
- Medicine and Medical Research