Open AccessTranscriptional Regulation of PIK3CA Oncogene by NF-κB in Ovarian Cancer Microenvironment
Author(s) -
Nuo Yang,
Jia Huang,
Joel Greshock,
Shun Liang,
Andrea Barchetti,
Kosei Hasegawa,
Sarah Kim,
Antonis Giannakakis,
Chunsheng Li,
Anne O'Brien-Jenkins,
Dionyssios Katsaros,
Ralf Bützow,
George Coukos,
Lin Zhang
Publication year - 2008
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0001758
Subject(s) - downregulation and upregulation , tumor microenvironment , cancer research , carcinogenesis , oncogene , biology , mechanism (biology) , ovarian cancer , in vivo , ovarian tumor , cancer , microbiology and biotechnology , cell cycle , tumor cells , genetics , gene , philosophy , epistemology
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-κB pathway. These results offer a new mechanism through which the tumor microenvironment directly activates oncogenic pathways in tumor cells.
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