title: Targeted expression of tumor necrosis factor-related apoptosis-inducing ligand TRAIL in skin protects mice against chemical carcinogenesis.
abstract: BACKGROUND
  Gene ablation studies have revealed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L, TNFSF10) plays a crucial role in tumor surveillance, as TRAIL-deficient mice exhibit an increased sensitivity to different types of tumorigenesis. In contrast, possible tumor-protective effect of increased levels of endogenous TRAIL expression in vivo has not been assessed yet. Such models will provide important information about the efficacy of TRAIL-based therapies and potential toxicity in specific tissues.
  
  
  METHODS
  To this aim, we engineered transgenic mice selectively expressing TRAIL in the skin and subjected these mice to a two-step chemical carcinogenesis protocol that generated benign and preneoplastic lesions. We were therefore able to study the effect of increased TRAIL expression at the early steps of skin tumorigenesis.
  
  
  RESULTS
  Our results showed a delay of tumor appearance in TRAIL expressing mice compared to their wild-type littermates. More importantly, the number of tumors observed in transgenic animals was significantly lower than in the control animals, and the lesions observed were mostly benign. Interestingly, Wnt/β-catenin signaling differed between tumors of wild-type and TRAIL transgenics.
  
  
  CONCLUSIONS
  Altogether, these data reveal that, at least in this model, TRAIL is able on its own to act on pre-transformed cells, and reduce their tumorigenic potential.
authors.affiliation: Department of Cancer Biology, Institut Génétique de Biologie Moléculaire et Cellulaire (IGBMC), France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kedinger
authors.forename: Stephanie
authors.initials: S
authors.lastname: Muller
authors.forename: Hinrich
authors.initials: H
authors.lastname: Gronemeyer
mesh_terms: D000818:Animals; D001551:Benz(a)Anthracenes; D049109:Cell Proliferation; D005260:Female; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053547:Keratin-14 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D001551:Benz(a)Anthracenes; D053547:Keratin-14; D053221:TNF-Related Apoptosis-Inducing Ligand; D051153:Wnt Proteins; D051176:beta Catenin; C046810:7,12-dihydroxymethylbenz(a)anthracene; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D013755:Tetradecanoylphorbol Acetate