Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are refractory to transformation by oncogenic H-Ras

Kristi L Berger; Felicia Barriga; Michael J Lace; Lubomir P Turek; Gideon J Zamba; Frederick E Domann; John H Lee; Aloysius J Klingelhutz

doi:10.1016/j.virol.2006.07.039

$Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are refractory to transformation by oncogenic H-Ras$

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Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are refractory to transformation by oncogenic H-Ras

Kristi L Berger, Felicia Barriga, Michael J Lace, Lubomir P Turek, Gideon J Zamba, Frederick E Domann, John H Lee and Aloysius J Klingelhutz

Virology (New York, N.Y.), Vol.356(1), pp.68-78

2006

DOI: 10.1016/j.virol.2006.07.039

PMCID: PMC1993897

PMID: 16945398

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Abstract

Ras expression in human epithelial cells with integrated HPV genomes has been shown to cause tumorigenic transformation. The effects of Ras in cells representing early stage HPV-associated disease (i.e., when HPV is extrachromosomal and the oncogenes are under control of native promoters) have not been examined. Here, we used human cervical keratinocyte cell lines containing stably replicating extrachromosomal HPV-16 and present the novel finding that these cells resist transformation by oncogenic H-Ras. Ras expression consistently diminished anchorage-independent growth (AI), reduced E6 and E7 expression, and caused p53 induction in these cells. Conversely, AI was enhanced or maintained in Ras-transduced cervical cells that were immortalized with a 16E6/E7 retrovirus, and minimal effects on E6 and E7 expression were observed. Ras expression with either episomal HPV-16 or LXSN-E6/E7 was insufficient for tumorigenic growth suggesting that other events are needed for tumorigenic transformation. In conclusion, our results indicate that Ras-mediated transformation depends on the context of HPV oncogene expression and that this is an important point to address when developing HPV tumor models.

Papillomavirus

Episomal HPV

Transformation

Anchorage independence

Ras

Cervical keratinocyte

Extrachromosomal

Episome

HPV

Details

Title: Subtitle: Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are refractory to transformation by oncogenic H-Ras
Creators: Kristi L Berger - Department of Microbiology, Holden Comprehensive Cancer Research Center, University of Iowa, 375 Newton Road, 2202 MERF, Iowa City, IA 52242, USA
Felicia Barriga - Department of Microbiology, Holden Comprehensive Cancer Research Center, University of Iowa, 375 Newton Road, 2202 MERF, Iowa City, IA 52242, USA
Michael J Lace - Veterans Affairs Medical Center, Iowa City, IA 52246, USA
Lubomir P Turek - Veterans Affairs Medical Center, Iowa City, IA 52246, USA
Gideon J Zamba - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
Frederick E Domann - Department of Radiology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242, USA
John H Lee - Department of Otolaryngology, Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Aloysius J Klingelhutz - Department of Microbiology, Holden Comprehensive Cancer Research Center, University of Iowa, 375 Newton Road, 2202 MERF, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Virology (New York, N.Y.), Vol.356(1), pp.68-78
DOI: 10.1016/j.virol.2006.07.039
PMID: 16945398
PMCID: PMC1993897
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: Elsevier Inc
Language: English
Date published: 2006
Academic Unit: Radiology; Microbiology and Immunology; Pathology; Biostatistics; Surgery; Radiation Oncology
Record Identifier: 9983997461202771

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