Quercetin elevates p27Kip1 and arrests both primary and HPV16 E6/E7 transformed human keratinocytes in G1

Beniston, R.G. and Campo, M.S. (2003) Quercetin elevates p27Kip1 and arrests both primary and HPV16 E6/E7 transformed human keratinocytes in G1. Oncogene, 22(35), pp. 5504-5514. (doi: 10.1038/sj.onc.1206848)

Abstract

Our previous work with primary bovine fibroblasts demonstrated that quercetin, a potent mutagen found in high levels in bracken fern (Pteridium aquilinum), arrested cells in G1 and G2/M, in correlation with p53 activation. The expression of bovine papillomavirus type 4 (BPV-4) E7 overcame this arrest and lead to the development of tumorigenic cells lines (Beniston et al., 2001). Given the possible link between papillomavirus infection, bracken fern in the diet and cancer of the upper gastrointestinal (GI) tract in humans, we investigated whether a similar situation would occur in human cells transformed by human papillomavirus type 16 (HPV-16) oncoproteins. Quercetin arrested primary human foreskin keratinocytes in G1. Arrest was linked to an elevation of the cyclin-dependent kinase inhibitor (cdki) p27Kip1. Expression of the HPV16 E6 and E7 oncoproteins in transformed cells failed to abrogate cell cycle arrest. G1 arrest in the transformed cells was also linked to an increase of p27Kip1 with a concomitant reduction of cyclin E-associated kinase activity. This elevation of p27Kip1 was due not only to increased protein half-life, but also to increased mRNA transcription.

• Item Type: Articles
• Keywords: HFK; HPV E6/E7; quercetin; cell cycle; p27Kip1
• 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; S Agriculture > SF Animal culture > SF600 Veterinary Medicine; R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Oncogene
• Publisher: Nature Publishing Group
• ISSN: 0950-9232
• Copyright Holders: Copyright © 2003 Nature Publishing Group
• First Published: First published in Oncogene 22(35):5504-5514
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher