Characterization of the Mechanisms of IGF-I-Mediated Stress-Activated Protein Kinase Activation in Human Breast Cancer Cell MCF-7

Abstract

Abstract : Specific aims: Insulin-like growth factors (IGFs) have been shown to stimulate cell proliferation and differentiation. And IGF-I, one of the important members of the IGF family plays an important role in the mitogenesis of breast cancer. IGF-I stimulates cell division by modulating events that occur during the early G1 phase. Cell proliferation and activation of oncogenes in cancer cells has been shown to be involved in the modulation of signal transduction pathways. The most important signal transduction pathways in mammalian cells are MAPK pathways, which include ERKl/ERK2, JNK and p38 pathways. These kinases are activated by growth factors and also under stress conditions. Amino acid starvation in cell lines can be used as an experimental model for stress, which can mimic the pathophysiological condition that results from protein deprivation during cancer cachexia. Therefore, we hypothesize that signal transduction pathways in human breast cancer are involved in IGF-I-mediated cellular proliferation under amino acid starvation conditions. Therefore, the specific aim of this study was designated to test the hypothesis that: The signal transduction pathways in human breast cancer involve activation of MAPK (ERKl/ERK2) and JNK pathways.