Involvement of NF-kappaB and AP-1 in COX-2 upregulation by human papillomavirus 16 E5 oncoprotein.
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.
Kim
Su-Hyeong
SH
Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Ku, Seoul 110-744, Korea.
Oh
Jung-Min
JM
No
Jae-Hong
JH
Bang
Yung-Jue
YJ
Juhnn
Yong-Sung
YS
Song
Yong-Sang
YS