Transcriptional regulation of PIK3CA oncogene by NF-κB in ovarian cancer microenvironment

Abstract

PIK3CA upregulation, amplification and mutation have been widely reported in ovarian cancers and other tumors, which strongly suggest that PIK3CA is a promising therapeutic target. However, to date the mechanisms underlying PIK3CA regulation and activation in vivo is still unclear. During tumorigenesis, host-tumor interactions may play a critical role in editing the tumor. Here, we report a novel mechanism through which the tumor microenvironment activates the PIK3CA oncogene. We show that PIK3CA upregulation occurs in non-proliferating tumor regions in vivo. We identified and characterized the PIK3CA 5′ upstream transcriptional regulatory region and confirmed that PIK3CA is transcriptionally regulated through NF-κB pathway. These results offer a new mechanism through which the tumor microenvironment directly activates oncogenic pathways in tumor cells. © 2008 Yang et al.