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Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Academic Health Center
Masonic Cancer Center

PI: Douglas Yee

Profiling the Role of IRS Proteins in Breast Cancer Through Gene Expression Analysis

The insulin-like growth factor (IGF) pathway mediates aberrant function during the initiation and progression of primary tumors and secondary metastases in cancer. As a result, a host of tyrosine kinase inhibitors and monoclonal antibodies directed against the type 1 IGF receptor (IGF-1R) have entered clinical trials with early positive results. However, no predictive biomarkers have yet emerged from these initial studies. These researchers propose that expanding IGF biomarkers beyond IGF-1R alone may identify the most appropriate candidates for anti-IGF therapy. Previous work has shown that the insulin receptor substrate (IRS) proteins serve as the functional link between IGF-I-induced IGF-1R phosphorylation and downstream signaling linked to cellular behavior. This work has demonstrated that IRS isoforms differentially mediate IGF-I action, whereby IRS-1 drives proliferation and IRS-2 triggers motility. The data suggest that IGF stimulation of breast cancer cells results in distinct profiles of gene expression that are dependent on IRS adaptor protein expression. In addition, some of the "IRS-regulated” genes are shared in common with other gene signatures of poor prognosis. With the use of anti-IGF therapies in breast cancer, attention should focus on the use of these profiles as prognostic and predictive biomarkers.

Group Member

Mark Becker, Graduate Student