Regulation of the Human MYC Proximal Promoter by STAT Proteins in Cancer Cells

Abstract

Accumulating evidence has indicated important roles played by Signal Transducer and Activator of Transcription (STAT) molecules, STAT1, STAT3 and STAT5 in the abnormal growth of cancer cells. Associated with these malignant changes, many of the STAT-target genes involved in cell growth regulation also become deregulated in cancer cells. One very important oncogene overexpressed in many cancers is MYC whose gene promoter has previously been found to be STAT regulated. Gene reporter assays provide useful tools for studying the roles of cytokines such as interferon (IFN) and their activation of STAT-dependent promoters. The aims of this study were to: 1) establish luciferase reporter vectors for evaluating STAT-mediated gene regulation; 2) investigate the differential DNA binding of STAT1 versus STAT3 and their sequence recognition and relate this to the regulation of key genes involved in malignancy, such as MYC; and 3) investigate the role of STAT5 in the regulation of the MYC promoter, given preliminary data which indicated STAT5 might be directly involved.