Validation of an HPV16-mediated carcinogenesis mouse model

In Vivo. 2014 Sep-Oct;28(5):761-7.

Abstract

Background/aim: Human papillomavirus Type 16 (HPV16) infection is a necessary but alone insufficient cause of invasive cervical cancer (ICC) and likely causes other genital cancers. Individual genetic variability influences the natural history of the neoplasm. Developing a variety of animal models to investigate HPV16-mediated carcinogenesis is important to Phase 1 trials for human cancer treatments.

Materials and methods: C57BL/6 mice expressing the HPV16-E7 transgene were treated with 100 nmoles of 7,12-dimethylbenz(a)anthracene (DMBA) on dorsal-thoracolumbar skin for ≤20 weeks.

Results: Transgenic-HPV16E7 mice showed more tumors (14.11±1.49 vs. 7.2±0.73) that more quickly reached maximal size (17.53±0.53 vs. 28.75±0.67 weeks) than syngeneic controls.

Conclusion: DMBA topically-treated C57BL/6-HPV16E7 mice developed chronic inflammation as well as benign and malignant lesions, many of which ulcerated. Histology showed that the HPV16-E7 transgene more than doubled the effect of complete carcinogenesis against a C57BL/6 background alone, strongly influencing the number, size, and time-to-maximal tumor burden for DMBA-exposed transgenic-C57BL/6 mice.

Keywords: 7,12-dimethylbenz(a)anthracene (DMBA); HPV type 16 (HPV16); HPV16E7; mice; transgenic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / administration & dosage
  • 9,10-Dimethyl-1,2-benzanthracene / adverse effects
  • Animals
  • Biopsy
  • Carcinogens / administration & dosage
  • Cell Transformation, Viral*
  • Disease Models, Animal
  • Female
  • Human papillomavirus 16* / genetics
  • Humans
  • Mice
  • Mice, Transgenic
  • Neoplasms / etiology*
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections / complications*
  • Tumor Burden

Substances

  • Carcinogens
  • Papillomavirus E7 Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • 9,10-Dimethyl-1,2-benzanthracene