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Related Experiment Videos

The mouse skin carcinogenesis model

T J Slaga1, I V Budunova, I B Gimenez-Conti

  • 1Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Smithville 78957, USA.

The Journal of Investigative Dermatology. Symposium Proceedings
|April 1, 1996
PubMed
Summary
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Skin tumor progression involves genetic changes and cell expansion. Alpha-glutamyl transpeptidase (GGT) expression drives malignant tumor formation and growth, indicating its critical role in advancing skin cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Skin carcinogenesis is a multistage process including initiation, promotion, and progression.
  • Tumor promoters expand initiated stem cells, correlating with hyperplasia.
  • Genetic alterations, such as trisomies 6 and 7, mark tumor progression from diploid to aneuploid states.

Purpose of the Study:

  • To investigate the role of alpha-glutamyl transpeptidase (GGT) in skin tumor progression.
  • To identify molecular markers associated with skin tumor progression.
  • To explore the involvement of telomerase and connexins in skin tumor progression.

Main Methods:

  • Transfection of functional GGT cDNA into papilloma-forming cell lines.
  • Subcutaneous injection and grafting of transfected cells into nude mice.

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  • Analysis of GGT expression, genomic status, telomerase activity, and connexin levels.

    • Main Results:

    • GGT-transfected cells formed malignant tumors upon subcutaneous injection, unlike control cells.
    • GGT-transfected cell grafts showed significantly increased mass compared to controls.
    • Increased telomerase activity and altered connexin expression (Cx26, Cx43, Cx31.1) correlated with tumor progression and genomic instability.

    Conclusions:

    • Alpha-glutamyl transpeptidase (GGT) plays a critical role in driving skin tumor progression towards malignancy.
    • Specific molecular markers, including GGT, keratin 13, keratins 1 and 10, telomerase, and connexins, are indicative of tumor progression.
    • Susceptibility to skin tumor promotion and progression may be independent processes.