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Chemical skin carcinogenesis is prevented in mice by the induced expression of a TGF-beta related transgene.

Publication ,  Journal Article
Blessing, M; Nanney, LB; King, LE; Hogan, BL
Published in: Teratog Carcinog Mutagen
1995

Skin papillomas and squamous cell carcinomas (SCCs) are induced in mice by tumor initiation with a carcinogen followed by tumor promotion with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). These usually arise from preneoplastic lesions characterized by epidermal proliferation and hyperplasia, dermal edema, and inflammation. To evaluate the role of polypeptide growth factors in chemically induced skin carcinogenesis, we used transgenic mice carrying the cDNA for a TGF-beta related molecule, bone morphogenetic protein-4 (BMP-4), under the control of the regulatory elements of the cytokeratin IV* gene in a skin carcinogenesis protocol. Control non-transgenic littermates and BMP-4 transgenic mice were treated with a single dose of a carcinogen, N-methyl-N'-nitrosoguanidine (MNNG), and biweekly with the tumor promoter TPA for 9 months. In control littermates TPA induced epidermal hyperproliferation, atypia with "dark" cells, and dermal inflammation, resulting in papillomas and SCCs in 13 of 26 animals tested. In BMP-4 transgenic mice, TPA treatment induced the expression of the BMP-4 transgene in interfollicular epidermis but only minimal epidermal thickening, hyperproliferation, and inflammation were noted after the initial dose of TPA. Furthermore, the mitotic indices in transgenic epidermis after 9 months of TPA treatment were significantly lower than the corresponding indices from untreated transgenic epidermis. Consequently, none of the 22 transgenic animals tested developed papillomas or SCCs. In conclusion, we have shown that the TPA induced expression of the BMP-4 transgene blocks proliferation and inflammation in skin, steps that are critical to the subsequent formation of papillomas and SCCs and we characterized an inducible promotersystem which expresses polypeptides in interfollicular epidermis after exogenous stimulation.

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Published In

Teratog Carcinog Mutagen

DOI

ISSN

0270-3211

Publication Date

1995

Volume

15

Issue

1

Start / End Page

11 / 21

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Toxicology
  • Tetradecanoylphorbol Acetate
  • Skin Neoplasms
  • Skin
  • Proteins
  • Papilloma
  • Mice, Transgenic
  • Mice
  • Methylnitronitrosoguanidine
 

Citation

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Blessing, M., Nanney, L. B., King, L. E., & Hogan, B. L. (1995). Chemical skin carcinogenesis is prevented in mice by the induced expression of a TGF-beta related transgene. Teratog Carcinog Mutagen, 15(1), 11–21. https://doi.org/10.1002/tcm.1770150103
Blessing, M., L. B. Nanney, L. E. King, and B. L. Hogan. “Chemical skin carcinogenesis is prevented in mice by the induced expression of a TGF-beta related transgene.Teratog Carcinog Mutagen 15, no. 1 (1995): 11–21. https://doi.org/10.1002/tcm.1770150103.
Blessing M, Nanney LB, King LE, Hogan BL. Chemical skin carcinogenesis is prevented in mice by the induced expression of a TGF-beta related transgene. Teratog Carcinog Mutagen. 1995;15(1):11–21.
Blessing, M., et al. “Chemical skin carcinogenesis is prevented in mice by the induced expression of a TGF-beta related transgene.Teratog Carcinog Mutagen, vol. 15, no. 1, 1995, pp. 11–21. Pubmed, doi:10.1002/tcm.1770150103.
Blessing M, Nanney LB, King LE, Hogan BL. Chemical skin carcinogenesis is prevented in mice by the induced expression of a TGF-beta related transgene. Teratog Carcinog Mutagen. 1995;15(1):11–21.

Published In

Teratog Carcinog Mutagen

DOI

ISSN

0270-3211

Publication Date

1995

Volume

15

Issue

1

Start / End Page

11 / 21

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Toxicology
  • Tetradecanoylphorbol Acetate
  • Skin Neoplasms
  • Skin
  • Proteins
  • Papilloma
  • Mice, Transgenic
  • Mice
  • Methylnitronitrosoguanidine