title: Expression of APC protein during tongue malignant transformation in galectin-3-deficient mice challenged by the carcinogen 4-nitroquniline-n-oxide.
abstract: Galectin-3 (Gal3) has been implicated in the development of different tumors because of its involvement in the Wnt signaling pathway by promoting beta-catenin translocation into the nucleus. The APC protein, a negative regulator of this pathway, has been strongly implicated in the development of colon cancer, but still has an undetermined role in the formation of oral cancer. Therefore, this study aimed to evaluate the relationship between Gal3, the Wnt signaling pathway, and APC expression in dysplasias and carcinomas developed experimentally in mice. Sixty galectin-3-deficient (Gal3(-/-)) and 60 wild-type (Gal3(+/+)) mice were early employed to be treated with the carcinogen 4NQO for 16 weeks and killed at either week 16 or week 32. Tongues were removed, processed and embedded in paraffin blocks. Sections 5 μm thick were made, and then stained by H&E to establish the diagnosis of dysplasia and carcinoma. Sections of 2 μm thickness were made to detect APC expression in these lesions by immunohistochemistry. Oral carcinogenesis occurred in both groups of mice, but no statistical difference was reached. APC expression was exclusively seen in the cytoplasm of all lesions studied. In the intragroup analysis, the majority of dysplasias and carcinomas exhibiting higher APC immunoreactivity was observed in Gal3(-/-) mice compared to Gal3(+/+) mice, but no significant difference was found. However, a statistical difference was only observed between dysplastic lesions from two mice. Our results showed that neither the absence of Gal3 nor the APC protein appears to play a role in malignant transformation of the tongue.
authors.affiliation: School of Medicine, Uberlândia Federal University Uberlândia, Brazil.
authors.forename: Marcus Vinicius Rodrigues
authors.initials: MV
authors.lastname: de Souza
authors.affiliation: Department of Morphology, Biomedical Science Institute, Uberlândia Federal University Uberlândia, Brazil.
authors.forename: João Paulo Silva
authors.initials: JP
authors.lastname: Servato
authors.affiliation: School of Dentistry, Uberlândia Federal University Uberlândia, Brazil.
authors.forename: Adriano Mota
authors.initials: AM
authors.lastname: Loyola
authors.affiliation: School of Dentistry, Uberlândia Federal University Uberlândia, Brazil.
authors.forename: Sérgio Vitorino
authors.initials: SV
authors.lastname: Cardoso
authors.affiliation: School of Medicine, São Paulo University São Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA, USA.
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.affiliation: Department of Morphology, Biomedical Science Institute, Uberlândia Federal University Uberlândia, Brazil.
authors.forename: Marcelo José Barbosa
authors.initials: MJ
authors.lastname: Silva
authors.affiliation: Department of Morphology, Biomedical Science Institute, Uberlândia Federal University Uberlândia, Brazil.
authors.forename: Paulo Rogério
authors.initials: PR
authors.lastname: de Faria
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D037502:Galectin 3 / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D002273:Carcinogens; D037502:Galectin 3; D015112:4-Nitroquinoline-1-oxide
keywords: APC protein; Oral carcinogenesis; galectin-3; immunohistochemistry; mice; tongue