HPV-16 oncogenes E6 and E7 are mutagenic in normal human oral keratinocytes

Oncogene
X LiuN H Park

Abstract

The mutation frequency of pS189 shuttle vector plasmids is higher in human oral keratinocytes (NHOK) immortalized with cloned human papillomavirus-16 (HPV-16) genome than in primary normal NHOK (NHOK). To determine whether oncoproteins E6 and E7 of HPV-16 are responsible for the higher mutation frequency of the plasmids, we measured the mutation frequency in NHOK and in NHOK expressing the HPV-16 oncogenes (E6, E7, or E6 plus E7). We also measured the mutation frequency in NHOK expressing the E6 or E7 proteins of the non-oncogenic HPV-6b. The mutation frequency, either background or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced, in NHOK expressing the HPV-16 oncoproteins (E6, E7, or E6 plus E7) was significantly higher than in NHOK. The HPV-16 oncogenes did not alter the nature of the MNNG-induced mutations (G:C-->A:T), but increased the frequency of deletions and insertions with or without MNNG. The background or MNNG-induced mutation frequency in NHOK expressing the HPV-6b E6 or E7 proteins was the same as in NHOK. NHOK and NHOK expressing HPV6b-E6 or E7 were able to arrest the cell cycle and enhance cellular p53, p21(WAF1/CIP1), and Gadd45 levels when exposed to MNNG, whereas NHOK expressing the HPV-16 E6 oncogene did ...Continue Reading

Citations

Mar 15, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Giovanni AlmadoriMaurizio Maurizi
Nov 12, 1998·Journal of the National Cancer Institute·S M SchwartzD A Galloway
Dec 2, 1998·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·S O IbrahimA C Johannessen
Jul 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·S HietanenD P Lane
Sep 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Katerina StratiPaul F Lambert
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·L M Alvarez-SalasJ A DiPaolo
Jul 28, 2011·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·H H SudhoffP K C Goon
Jan 30, 2004·International Journal of Cancer. Journal International Du Cancer·Stefan Duensing, Karl Münger
Mar 28, 2009·Environmental and Molecular Mutagenesis·Anette DuensingStefan Duensing
Nov 16, 2010·Cancer Letters·Nina KorzeniewskiStefan Duensing
Jul 31, 2004·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·Patrick K Ha, Joseph A Califano
Jun 24, 2008·Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews·Adriana Báez
Jun 30, 2000·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·M BoudaC Kittas
Jan 9, 2020·International Journal of Oral Science·Hannah S HongKi-Hyuk Shin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.