HPV-18 transformed cells fail to arrest in G1 in response to quercetin treatment

Beniston, R.G. and Campo, M.S. (2005) HPV-18 transformed cells fail to arrest in G1 in response to quercetin treatment. Virus Research, 109(2), pp. 203-209. (doi: 10.1016/j.virusres.2004.12.002)

Abstract

Previous work with primary human keratinocytes demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (Pteridium aquilinum), arrested cells in G1 with concomitant elevation of the cyclin-dependent kinase inhibitor (cdki) p27Kip1. Expression of the human papillomavirus type 16 (HPV-16) E6 and E7 oncoproteins, under transcriptional control of a heterologous promoter, in transformed keratinocytes failed to abrogate this arrest [Beniston, R., Campo, M.S., 2003. Quercetin elevates p27(Kip1) and arrests both primary and HPV-16 E6/E7 transformed human keratinocytes in G1. Oncogene 22, 5504–5514]. Given the link between papillomavirus infection, bracken fern in the diet and cancer of the oesophagus in humans, we wished to investigate further whether cells transformed by the whole genome of HPV-16 or HPV-18, with E6 and E7 under the transcriptional control of their respective homologous promoters, would be similarly arrested in G1 by quercetin. In agreement with earlier work, quercetin arrested HPV-16 transformed cells in G1 with an increase in the cyclin-dependent kinase inhibitor p27Kip1. However, HPV-18 transformed cells did not arrest after quercetin treatment. The failure of HPV-18 transformed cells to arrest in G1 was linked to the up-regulation of the HPV-18 long control region (LCR) by quercetin, maintaining high expression of the viral transforming proteins. Transcriptional up-regulation of the HPV-18 LCR was mediated by a “quercetin responsive element” homologous to the one identified previously in the bovine papillomavirus type 4 (BPV-4) LCR.

• Item Type: Articles
• Keywords: Quercetin, HPV, p27Kip1, LCR
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Campo, Professor Saveria
• Authors: Beniston, R.G., and Campo, M.S.
• Subjects: Q Science > QR Microbiology > QR180 Immunology; S Agriculture > SF Animal culture > SF600 Veterinary Medicine
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Virus Research
• Publisher: Elsevier Science
• ISSN: 0168-1702
• Copyright Holders: Copyright © 2005 Elsevier Science
• First Published: First published in Virus Research 109(2):203-209
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher