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- Title
Transcriptional Regulation of PIK3CA Oncogene by NFκB in Ovarian Cancer Microenvironment.
- Authors
Nuo Yang; Jia Huang; Greshock, Joel; Shun Liang; Barchetti, Andrea; Hasegawa, Kosei; Kim, Sarah; Giannakakis, Antonis; Chunsheng Li; O'Brien-Jenkins, Anne; Katsaros, Dionyssios; Bützow, Ralf; Coukos, George; Lin Zhang
- 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 59 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.
- Subjects
OVARIAN tumors; ONCOGENES; CARCINOGENESIS; TUMORS; CANCER invasiveness; CANCER cell growth
- Publication
PLoS ONE, 2008, Vol 3, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0001758