The roles of Smad2 and Smad3 in the development of chemically induced skin tumors in mice.
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.
Tannehill-Gregg
S H
SH
Department of Molecular Genetics, Division of Human Cancer Genetics, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA.
Kusewitt
D F
DF
Rosol
T J
TJ
Weinstein
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D006652:Histological Techniques; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010212:Papilloma / Q000139:chemically induced* / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D002273:Carcinogens; D004268:DNA-Binding Proteins; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D015127:9,10-Dimethyl-1,2-benzanthracene