Involvement of NF-kappaB and AP-1 in COX-2 upregulation by human papillomavirus 16 E5 oncoprotein

Carcinogenesis. 2009 May;30(5):753-7. doi: 10.1093/carcin/bgp066. Epub 2009 Mar 25.


The human papillomavirus (HPV) E6 and E7 oncoproteins play important roles in cervical carcinogenesis through multiple mechanisms, including upregulation of cyclooxygenase-2 (COX-2), which has been shown to be involved in both carcinogenesis and cancer progression. To explore the role of E5 in cervical carcinogenesis, we herein investigated the effect of HPV 16 E5 on COX-2 expression. Our results revealed that E5 induced COX-2 expression through the epidermal growth factor receptor-signaling pathway, with nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) acting as critical factors in E5-induced COX-2 expression. NF-kappaB inhibition blocked COX-2 expression more potently than inhibition of AP-1. Our findings collectively suggest that the HPV 16 E5 oncoprotein mediates cervical carcinogenesis at least in part via upregulation of COX-2 expression through NF-kappaB and AP-1, with NF-kappaB playing a larger role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Culture Media
  • Cyclooxygenase 2 / genetics*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Human papillomavirus 16 / physiology
  • Humans
  • Kidney / embryology
  • NF-kappa B / physiology*
  • Oncogene Proteins, Viral / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor AP-1 / physiology*
  • Transfection
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / virology


  • Culture Media
  • NF-kappa B
  • Oncogene Proteins, Viral
  • Transcription Factor AP-1
  • oncogene protein E5, Human papillomavirus type 16
  • Cyclooxygenase 2