Transcriptional Regulation of PIK3CA Oncogene by NF-κB in Ovarian Cancer Microenvironment

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:
  • PLoS ONE

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2008