Transcriptional regulation of PIK3CA oncogene by NF-kappaB in ovarian cancer microenvironment.
basic_science · Level V
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- Record sourced from PubMed, PMID 18335034.
- Also identified by DOI 10.1371/journal.pone.0001758 and PMC identifier PMC2857533.
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Abstract
PIK3CA upregulation, amplification and mutation have been widely reported in ovarian cancers and other tumors, which strongly suggests 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-kappaB pathway. These results offer a new mechanism through which the tumor microenvironment directly activates oncogenic pathways in tumor cells.