The mouse skin carcinogenesis model

Thomas J Slaga, Irina V. Budunova, Irma B. Gimenez-Conti, C. Marcelo Aldaz

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Skin carcinogenesis can be divided into at least three major stages: initiation, promotion, and progression. In the mouse skin model, the first stage is thought to involve the interaction of a tumor initiator with the genetic material of stem cells, leading to an irreversible alteration in growth control or differentiation, probably by activation of the Un-ras oncogene. The major effect of all skin-tumor promoters seems to be the specific expansion of the initiated stem cells. The correlation between the abilities of tumor promoters to induce sustained hyperplasia and their tumorpromoting activities is very good. We found that the appearance of a-glutamyl transpeptidase (GGT) and keratin 13 and the lack of expression of keratins 1 and 10 are good markers for skin tumor progression. These alterations occur when papillomas change from a diploid to an aneuploid state, mainly as a result of developing trisomies 6 and 7. To evaluate the role of GGT in skin-tumor progression, we transfected a functional GGT cDNA into two cell lines that normally produce papillomas when grafted into the skin of nude mice. When injected subcutaneously, all of the GGT-transfected clones formed malignant tumors, whereas only 24% of vector-transfected cells did. When GGT-transfected clones were placed into grafts, the grafts had an average mass almost three times that of grafts of vector-transfected cells. Our recent studies also suggest that the ribonucleoprotein telomerase and the gap-junctional proteins connexins (Cxs) are also important in skin-tumor progression. A progressive increase in telomerase activity was associated with the increased level of genomic instability during tumor progression. In addition, the level and expression of Cx26, Cx43, and Cx31.1 were significantly altered during skin tumor promotion and progression. The differences of various mouse stocks and strains in susceptibility to multistage skin carcinogenesis seem to be related more to alterations in tumor promotion than to tumor initiation; however, the critical events have not been determined. Results with an inbred strain of SENCARmice, which are very sensitive to papilloma formation by the two-stage protocol, also suggest that susceptibility is related to promotion. Despite the high incidence of papillomas in these inbred SENCAR mice, the number of malignant tumors was extremely low, suggesting that sensitivity to promotion and progression are independent in these mice.

Original languageEnglish (US)
Pages (from-to)151-156
Number of pages6
JournalJournal of Investigative Dermatology Symposium Proceedings
Volume1
Issue number2
StatePublished - 1996
Externally publishedYes

Fingerprint

Carcinogenesis
Skin
Papilloma
Neoplasms
Carcinogens
Telomerase
Transplants
Keratin-13
Inbred SENCAR Mouse
Stem Cells
Keratin-1
Keratin-10
Clone Cells
Connexin 43
Connexins
Ribonucleoproteins
ras Genes
gamma-Glutamyltransferase
Genomic Instability
Trisomy

Keywords

  • Initiation
  • Papillomasl
  • Progressionl
  • Promotionl
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Dermatology

Cite this

Slaga, T. J., Budunova, I. V., Gimenez-Conti, I. B., & Marcelo Aldaz, C. (1996). The mouse skin carcinogenesis model. Journal of Investigative Dermatology Symposium Proceedings, 1(2), 151-156.

The mouse skin carcinogenesis model. / Slaga, Thomas J; Budunova, Irina V.; Gimenez-Conti, Irma B.; Marcelo Aldaz, C.

In: Journal of Investigative Dermatology Symposium Proceedings, Vol. 1, No. 2, 1996, p. 151-156.

Research output: Contribution to journalArticle

Slaga, TJ, Budunova, IV, Gimenez-Conti, IB & Marcelo Aldaz, C 1996, 'The mouse skin carcinogenesis model', Journal of Investigative Dermatology Symposium Proceedings, vol. 1, no. 2, pp. 151-156.
Slaga TJ, Budunova IV, Gimenez-Conti IB, Marcelo Aldaz C. The mouse skin carcinogenesis model. Journal of Investigative Dermatology Symposium Proceedings. 1996;1(2):151-156.
Slaga, Thomas J ; Budunova, Irina V. ; Gimenez-Conti, Irma B. ; Marcelo Aldaz, C. / The mouse skin carcinogenesis model. In: Journal of Investigative Dermatology Symposium Proceedings. 1996 ; Vol. 1, No. 2. pp. 151-156.
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