The roles of Smad2 and Smad3 in the development of chemically induced skin tumors in mice

Vet Pathol. 2004 May;41(3):278-82. doi: 10.1354/vp.41-3-278.


Transforming growth factor-beta (TGF-beta) plays a complex role in skin carcinogenesis, acting as a suppressor early in tumor development but later as a promoter. Smad proteins are important intracellular mediators of TGF-beta signaling. To determine the effect of disrupting Smad genes and TGF-beta signaling on chemically induced skin carcinogenesis in mice, transgenic mice heterozygous for Smad2 or Smad3 deletions and wild-type controls were treated with topical dimethylbenzanthracene for 7 months. Tumor multiplicity, type, and degree of differentiation were assessed by histopathology and immunohistochemistry. Smad3(+/-) mice developed significantly fewer tumors than the wild-type group (P < 0.05). This indicated a possible oncogenic function for Smad3 in skin carcinogenesis. Smad2(+/-) mice formed less-differentiated tumors than their wild-type counterparts, supporting a tumor suppressor role for Smad2. There was a significant difference (P < 0.05) in tumor type between Smad2(+/-) and Smad3(+/-) groups, suggesting that Smad2 and Smad3 may regulate different targets.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Carcinogens
  • Carcinoma, Squamous Cell / chemically induced*
  • Carcinoma, Squamous Cell / metabolism
  • DNA-Binding Proteins / metabolism*
  • Disease Models, Animal
  • Histological Techniques
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Papilloma / chemically induced*
  • Papilloma / metabolism
  • Signal Transduction
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / metabolism
  • Smad2 Protein
  • Smad3 Protein
  • Trans-Activators / metabolism*
  • Transforming Growth Factor beta / metabolism


  • Carcinogens
  • DNA-Binding Proteins
  • Smad2 Protein
  • Smad2 protein, mouse
  • Smad3 Protein
  • Smad3 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta
  • 9,10-Dimethyl-1,2-benzanthracene