Regulation of the tyrosine phosphatase SHP-1 expression by C-jun-N-terminal kinase and RFX-1 and AP-4 transcription factors in insulin-like growth factor-1 (IGF-1) stimulated breast adenocarcinoma MCF-7 cells

Abstract

This thesis is devoted to reveal the negative regulators in IGF-1 (Insulin like growth factor 1) stimulated growth of a human breast adenocarcinoma cell line. It is a well established fact that increased circulating levels of IGF-1 correlate with increased risk of breast cancer. IGF-1 activation of its receptor, IGF-1R, is implicated in the progression of breast cancer, where IGF-1 stimulation leads to proliferative and anti-apoptotic responses by stimulating MAPK Erk and PI3K, respectively. In this study, IGF-1 stimulated MCF-7 cells proliferated more in the absence of MAPK JNK, implicating the involvement of MAPK JNK in the negative regulation of IGF-1 stimulated cell growth. In this research study, we show for the first time that IGF-1 stimulation of breast cancer cells induces SHP-1-expression by activating JNK, which in turn, activates RFX-1 and AP-4 transcription factors to allow them to bind to the high-expression region of the SHP-1 P-1 promoter in breast adenocarcinoma MCF-7 cells. (Abstract shortened by UMI.)