The role of human papillomavirus 16 E6 in anchorage-independent and invasive growth of mouse tonsil epithelium

Andrew C Hoover; William C Spanos; George F Harris; Mary E Anderson; Aloysius J Klingelhutz; John H Lee

doi:10.1001/archotol.133.5.495

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The role of human papillomavirus 16 E6 in anchorage-independent and invasive growth of mouse tonsil epithelium

Journal article

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The role of human papillomavirus 16 E6 in anchorage-independent and invasive growth of mouse tonsil epithelium

Andrew C Hoover, William C Spanos, George F Harris, Mary E Anderson, Aloysius J Klingelhutz and John H Lee

Archives of otolaryngology--head & neck surgery, Vol.133(5), pp.495-502

05/2007

DOI: 10.1001/archotol.133.5.495

PMCID: PMC2917346

PMID: 17515506

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Abstract

To provide a manipulatable system to study the mechanism of human papillomavirus 16 (HPV16) E6-related transformation of an epithelial cell type affected by HPV16 in humans. Biochemical and physiological studies of mouse tonsil epithelial cells (MTECs) transformed with HPV16 oncogenes plus H-ras in vitro and in vivo. Basic research laboratory. C57BL/6 mice. Transduction of the HPV16 oncogenes E6 and E7 in retroviral vectors into MTECs with isolation of multiple individual clones that expressed E6, E7, or both alone or in conjunction with H-ras. Growth in culture, anchorage-independent growth, and growth in immune competent, syngeneic mice. The MTECs that expressed E6 degraded p53 by a mechanism that is inhibited by proteasomal blockade. Although normal MTECs senesced after 20 population doublings, E6 alone or in combination with E7 was sufficient to immortalize MTECs beyond 25 population doublings, lower their population-doubling time, and permit anchorage-independent growth. However, only MTECs that express E6 plus H-ras or E6/E7 plus H-ras formed invasive tumors in immune competent, syngeneic mice at orthotopic intraoral and subdermal sites. We found that HPV16 E6 and E7 alone are not sufficient for invasive growth. However, the synergistic activity of H-ras and E6 was sufficient to result in invasive growth.

Transfection

Papillomavirus E7 Proteins

Tumor Suppressor Protein p53 - genetics

Cell Transformation, Neoplastic - genetics

Palatine Tonsil - metabolism

Oncogene Proteins, Viral - genetics

Tumor Cells, Cultured

Mouth Mucosa - pathology

Transduction, Genetic - methods

Repressor Proteins - metabolism

Genes, ras - genetics

Oncogene Proteins, Viral - metabolism

Epithelium - pathology

Genomic Islands - genetics

Epithelium - metabolism

Neoplasm Invasiveness

Mice, Inbred C57BL

Repressor Proteins - genetics

Cell Transformation, Neoplastic - metabolism

Epithelium - virology

Genetic Vectors - genetics

Mouth Mucosa - metabolism

Palatine Tonsil - pathology

Animals

Mouth Mucosa - virology

Palatine Tonsil - virology

Mice

Cell Transformation, Neoplastic - pathology

Details

Title: Subtitle: The role of human papillomavirus 16 E6 in anchorage-independent and invasive growth of mouse tonsil epithelium
Creators: Andrew C Hoover - Department of Otolaryngology-Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
William C Spanos
George F Harris
Mary E Anderson
Aloysius J Klingelhutz
John H Lee
Resource Type: Journal article
Publication Details: Archives of otolaryngology--head & neck surgery, Vol.133(5), pp.495-502
DOI: 10.1001/archotol.133.5.495
PMID: 17515506
PMCID: PMC2917346
NLM abbreviation: Arch Otolaryngol Head Neck Surg
ISSN: 0886-4470
eISSN: 1538-361X
Publisher: American Medical Association; United States
Grant note: R01 DE018386-05 / NIDCR NIH HHS R01 DE018386 / NIDCR NIH HHS
Language: English
Date published: 05/2007
Academic Unit: Microbiology and Immunology; Radiation Oncology
Record Identifier: 9984001213902771

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