Transcriptional regulation of PIK3CA oncogene by NF-kappaB in ovarian cancer microenvironment.
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.
Yang
Nuo
N
Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
Huang
Jia
J
Greshock
Joel
J
Liang
Shun
S
Barchetti
Andrea
A
Hasegawa
Kosei
K
Kim
Sarah
S
Giannakakis
Antonis
A
Li
Chunsheng
C
O'Brien-Jenkins
Anne
A
Katsaros
Dionyssios
D
Bützow
Ralf
R
Coukos
George
G
Zhang
Lin
L
D001483:Base Sequence; D058534:Class I Phosphatidylinositol 3-Kinases; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016328:NF-kappa B / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D014158:Transcription, Genetic
D017931:DNA Primers; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human