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Carcinogenesis Advance Access published online on March 25, 2009
Carcinogenesis, doi:10.1093/carcin/bgp066
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Involvement of NF-{kappa}B and AP-1 in COX-2 upregulation by Human Papillomavirus 16 E5 oncoprotein

Su-Hyeong Kim1, Jung-Min Oh1,2, Jae-Hong No1,4, Yung-Jue Bang1,3, Yong-Sung Juhnn1,2 and Yong-Sang Song1,4,*

1 Cancer Research Institute, Seoul National University College of Medicine
2 Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine
3 Department of Internal Medicine
4 Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Ku, Seoul 110-744 Korea

* Correspondence to: Yong-Sang Song, M.D.,Ph D. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea, Tel: 82-2-2072-2822, Fax: 82-2-3668-7401, E-mail: yssong{at}snu.ac.kr

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 EGFR signaling pathway, with nuclear factor-kappaB (NF-{kappa}B) and activator protein-1 (AP-1) acting as critical factors in E5-induced COX-2 expression. NF-{kappa}B 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-{kappa}B and AP-1, with NF-{kappa}B playing a larger role.

Key Words: HPV • E5 • COX-2 • NF-{kappa}B • AP-1

Received August 24, 2008; revised February 18, 2009; accepted March 18, 2009.


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