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Transcriptional Regulation of PIK3CA Oncogene by NF-κB 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 tumorigen...

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Detalles Bibliográficos
Autores principales: Yang, Nuo, Huang, Jia, Greshock, Joel, Liang, Shun, Barchetti, Andrea, Hasegawa, Kosei, Kim, Sarah, Giannakakis, Antonis, Li, Chunsheng, O'Brien-Jenkins, Anne, Katsaros, Dionyssios, Bützow, Ralf, Coukos, George, Zhang, Lin
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2258145/
https://www.ncbi.nlm.nih.gov/pubmed/18335034
http://dx.doi.org/10.1371/journal.pone.0001758
Descripción
Sumario: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.