title: Hedgehog signaling pathway mediates tongue tumorigenesis in wild-type mice but not in Gal3-deficient mice.
abstract: Oral squamous cell carcinoma (OSCC) is one of the most aggressive cancers of the oral cavity and an important cause of death worldwide. Currently, there are limited clinical tools aiding clinicians to establish its early diagnosis, and genetic and epigenetic events leading to the pathogenesis of OSCC remain unsolved. The use of carcinogen-induced knocked out mouse models would help to improve its early detection and also determine the role of proteins such as galectin-3 (Gal3) in this process. Here we used a mouse model of oral carcinogenesis employing two mouse genotypes: wild-type (Gal3+/+) and galectin-3-deficient mice (Gal3-/-) challenged by the carcinogen 4NQO for 16 weeks. After induction, the expression of Wnt1, Wnt3A, Shh and Gli3 proteins in tongue samples was evaluated using an immunohistochemistry approach. All samples of dysplasia and carcinoma were negative for Wnt1. Wnt3A expression was detected in both Gal3+/+ and Gal3-/- mice, at similar levels. Wnt3A expression did not predict tongue tumorigenesis in either genotype. Dysplastic- and carcinoma-expressing Shh was statistically significantly higher in Gal3+/+ mice than Gal3-/- mice (p<0.0001), and was associated with tongue tumorigenesis only in the former. Gli3 expression decreased and increased from dysplasia to carcinoma in Gal3+/+ and Gal3-/- mice, respectively, although the difference was not significant. The results suggest that activated Wnt signaling is present in both mice, and that the Hh signaling pathway might play a role in tongue carcinoma development in Gal3+/+ mice.
authors.affiliation: Uberlândia Federal University, Biomedical Science Institute, Department of Morphology, Uberlândia, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: de Oliveira Santos
authors.affiliation: Uberlândia Federal University, School of Dentistry, Uberlândia, Brazil.
authors.forename: Adriano Mota
authors.initials: AM
authors.lastname: Loyola
authors.affiliation: Uberlândia Federal University, School of Dentistry, Uberlândia, Brazil.
authors.forename: Sérgio Vitorino
authors.initials: SV
authors.lastname: Cardoso
authors.affiliation: São Paulo University, School of Medicine, São Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, CA, USA.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.affiliation: Uberlândia Federal University, Biomedical Science Institute, Department of Morphology, Uberlândia, Brazil. Electronic address: paulorfaria@icbim.ufu.br.
authors.forename: Paulo Rogério
authors.initials: PR
authors.lastname: de Faria
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D037502:Galectin 3 / Q000172:deficiency / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology*; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D002273:Carcinogens; D037502:Galectin 3; D053823:Hedgehog Proteins
keywords: Galectin-3; Mice; Oral carcinogenesis; Sonic hedgehog; Tongue; Wnt signaling