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Cell Population Analyses During Skin Carcinogenesis
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Considerations for skin carcinogenesis experiments using inducible transgenic mouse models.

Martyna C Popis1, Rebecca E Wagner2, Fernando Constantino-Casas3

  • 1Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.

BMC Research Notes
|January 25, 2018
PubMed
Summary

This study investigated skin tumor progression in mice, finding that while papillomas frequently formed, they rarely advanced to squamous cell carcinomas (SCCs). Challenges include low malignant conversion rates and frequent mouth tumor development in this cancer model.

Keywords:
Mouse modelPapillomaSCCSkin carcinogenesisk-rasp53

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Area of Science:

  • Oncology
  • Dermatology
  • Genetics

Background:

  • Skin tumors, including papillomas and squamous cell carcinomas (SCCs), represent a significant area of oncological research.
  • Transgenic mouse models are crucial for studying carcinogenesis and evaluating potential therapeutic targets.
  • Understanding the progression from non-malignant to malignant skin lesions is key to developing effective cancer prevention and treatment strategies.

Purpose of the Study:

  • To estimate the rate of progression from non-malignant skin tumors (papillomas) to malignant squamous cell carcinomas (SCCs).
  • To evaluate the utility of established transgenic mouse models for skin carcinogenesis studies.
  • To identify challenges in using these models for studying skin cancer development.

Main Methods:

  • Utilized established transgenic mouse models with conditionally induced oncogenic point mutant alleles of p53 and k-ras.
  • Oncogenic transgenes were activated in epidermal basal cells via tamoxifen administration.
  • Papilloma formation and progression to SCCs were monitored following various tamoxifen delivery methods.

Main Results:

  • Over 80% of mice developed skin papillomas, predominantly around the mouth, after transgene activation.
  • Mouth papillomas often led to rapid weight loss and necessitated culling before SCC progression could be fully assessed.
  • Only one out of 18 mice with a slow-releasing tamoxifen pellet progressed to a malignant SCC, indicating a low conversion rate.

Conclusions:

  • The study highlights significant challenges in using this specific transgenic mouse model for skin carcinogenesis research.
  • Low conversion rates of papillomas to SCCs and a high incidence of mouth papilloma formation impede the study of SCC development.
  • Further refinement of experimental models is needed to accurately assess skin tumor progression to malignancy.