Differential Roles of Insulin Receptor Substrate-1 and -2 (IRS-1, IRS-2) in Insulin-Like Growth Factor Signaling in Breast Cancer Cells

摘要

Signaling of insulin-like growth factor-I (IGF-I) through the type I insulin-like growth factor receptor (IGF-IR) has been shown to regulate breast cancer cell proliferation, survival and metastasis in vitro. Recent evidence indicates insulin receptor substrate-1 and -2 (IRS-1 and IRS-2), the primary signaling molecules utilized by the IGF-IR, may mediate distinct IGF-I effects. To investigate the specific functional roles of the IRS species in mediating IGF action, we utilized the T47D-Y and T47D-YA breast cancer cell lines, which lack both IRS-1 and IRS-2 expression yet express a functional IGF-IR, to generate cell lines that independently express IRS-1 or IRS-2. T47D-Y and T47D-YA breast cancer cells were stably transfected with either human IRS-1 or IRS-2 cDNA, screened for IRS expression and activation by immunoblotting, and analyzed for IGF responsiveness in proliferation and motility assays.