Browse

Human papillomavirus E5 protein induces expression of the EP4 subtype of prostaglandin E2 receptor in cyclic AMP response element-dependent pathways in cervical cancer cells

Cited 40 time in Web of Science Cited 43 time in Scopus
Authors
Oh, Jung-Min; Kim, Su-Hyeong; Lee, Yun-Il; Seo, Miran; Kim, So-Young; Song, Yong-Sang; Kim, Woo-Ho; Juhnn, Yong-Sung
Issue Date
2008-10-14
Publisher
Oxford University Press
Citation
Carcinogenesis., 30(1), 141-149
Keywords
Base SequenceCell Line, TumorCyclic AMP/*metabolism/physiologyCyclic AMP Response Element-Binding Protein/physiologyCyclic AMP-Dependent Protein Kinases/metabolismCyclooxygenase 2/metabolismDNA PrimersDinoprostone/physiologyElectrophoretic Mobility Shift AssayFemaleHumansImmunohistochemistryLuminescenceOncogene Proteins, Viral/*physiologyPromoter Regions, GeneticRNA InterferenceReceptor, Epidermal Growth Factor/metabolismReceptors, Prostaglandin E/*geneticsReverse Transcriptase Polymerase Chain ReactionUterine Cervical Neoplasms/*metabolism/pathology
Abstract
Human papillomavirus (HPV) is the major cause of uterine cervical cancer, but the role of the HPV E5 in carcinogenesis is not clearly understood. Prostaglandins are known to contribute to carcinogenesis of cervical cancer, and we therefore investigated the effect of HPV16 E5 on the expression of prostaglandin E2 (PGE2) receptors and underlying mechanisms. Stable expression of the E5 induced expression of the EP4 subtype of PGE2 receptors in C33A cervical cancer cells, and transfection of E5 small interfering RNA (siRNA) decreased it. EP4 protein expression was increased in human cervical cancer tissues, and EP4 mediated E5-induced increase in anchorage-independent colony formation and vascular endothelial growth factor expression. E5 induced cyclooxygenase-2 (COX-2) expression, and COX-2 increased PGE2 secretion and EP4 expression. The induction of EP4 by PGE2 and E5 was inhibited by an EP4 antagonist, inhibitors of cyclic adenosine monophosphate-dependent protein kinase or phosphatidylinositol 3-kinase, and a cyclic adenosine monophosphate response element (CRE) decoy. E5 increased the luciferase expression controlled by a variant CRE of the EP4 promoter, and it also increased the binding of cyclic adenosine monophosphate response element binding protein (CREB) to oligonucleotides containing this CRE. We conclude that the HPV16 E5 protein induces EP4 receptor protein in cervical cancer cells and that this induction involves epidermal growth factor receptor, COX-2, PGE2, EP2 and EP4, protein kinase A, CREB and CRE.
ISSN
1460-2180 (Electronic)
Language
English
URI
http://carcin.oxfordjournals.org/cgi/reprint/30/1/141.pdf

http://hdl.handle.net/10371/67497
DOI
https://doi.org/10.1093/carcin/bgn236
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse