title: Wnt/beta-catenin signalling pathway following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.
abstract: The Wnt/beta-catenin signaling pathway plays an important role in development, tissue homeostasis, and regeneration. Inappropriate activation of the Wnt pathway is linked to a wide range of human cancers. The purpose of this study was to characterize the Wnt/beta-catenin signaling pathway as depicted by the expression of Wnt1, Frizzled-1, Wnt5a, Frizzled-5 and beta-catenin during 4NQO-induced rat tongue carcinogenesis by immunohistochemistry. Male Wistar rats were distributed into three groups of 10 animals each and treated with 4NQO solution at 50 ppm through their drinking water for 4, 12, and 20 weeks. Ten animals were used as control group. No histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure; however, an overexpression of Wnt5a was noticed when compared to control group (p<0.05). The Wnt1 showed significant differences (p<0.05) in pre-neoplastic lesions at 12 weeks following carcinogen exposure. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, Wnt1 was expressed in the majority of the dysplasic cells and tumor cells. This was statistically significant (p<0.05). No significant differences (p>0.05) were found in expression of Frizzled-1, Frizzled-5 or beta-catenin following oral carcinogenesis. Taken together, our results support the belief that expression of Wnt1 and Wnt5a is related to malignant transformation and conversion of oral mucosa.
authors.affiliation: Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
authors.forename: Ana Carolina Cuzzuol
authors.initials: AC
authors.lastname: Fracalossi
authors.forename: Marcelo de Souza
authors.initials: Mde S
authors.lastname: Silva
authors.forename: Celina Tijuko Fujiyama
authors.initials: CT
authors.lastname: Oshima
authors.forename: Daniel Araki
authors.initials: DA
authors.lastname: Ribeiro
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D002273:Carcinogens; C495268:Ctnnb1 protein, rat; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; C495245:Wnt1 protein, rat; C491837:Wnt5a protein, rat; D051176:beta Catenin; D015112:4-Nitroquinoline-1-oxide