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Int J Clin Exp Pathol 2012;5(6):547-554

Original Article
The inactive form of glycogen synthase kinase-3β is associated with the development of
carcinomas in galectin-3 wild-type mice, but not in galectin-3-deficient mice

Daniella Fernandes Mendonça, Roger Chammas, Fu-Tong Liu, Suely Nonogaki, Sergio Vitorino Cardoso, Adriano Mota Loyola, Paulo Rogério
de Faria

Uberlândia Federal University, School of Medicine, Uberlândia, Brazil; São Paulo University, School of Medicine, São Paulo, Brazil; Department
of Dermatology, University of California, Davis, School of Medicine, Sacramento, CA, USA; Adolfo Lutz Institute, Molecular and Quantitative
Pathology, São Paulo, Brazil; Uberlândia Federal University, School of Dentistry, Uberlândia, Brazil; Uberlândia Federal University, Biomedical
Science Institute, Department of Morphology, Uberlândia, Brazil

Received March 8, 2012; Accepted June 23, 2012; Epub July 17, 2012; Published August 15, 2012

Abstract: Galectin-3 has been implicated in the tumor development via its mediation of the Wnt signaling pathway. Likewise, glycogen
synthase kinase-3beta (GSK3β) also plays a role in the Wnt signaling pathway by controlling the levels of cytoplasmic beta-catenin. Altered
GSK3β expression has been described in various tumors, but to date, there are no studies evaluating its expression in models of oral
carcinogenesis. Additionally, it is unknown whether the absence of galectin-3 regulates the expression of GSK3β. To this end, Gal3-deficient
(Gal3-/-) and wild-type (Gal3+/+) male mice were treated with 4NQO for 16 weeks and sacrificed at week 16 and 32. The tongues were
removed, processed, and stained with H&E to detect dysplasias and carcinomas. An immunohistochemical assay was performed to
determine the level of P-GSK3β-Ser9 expression in both groups. Carcinomas were more prevalent in Gal3+/+ than Gal3-/- mice (55.5% vs.
28.5%), but no statistical difference was reached. In the dysplasias, the proportion of cells positive for P-GSK3β-Ser9 was slightly higher in
Gal3+/+ than Gal3-/- mice (63% vs. 61%). In the carcinomas, a significant difference between Gal3+/+ and Gal3-/- mice was found (74% vs.
59%; p=0.02). P-GSK3β-Ser9-positive cells slightly decreased from the progression of dysplasias to carcinomas in Gal3-/- mice (61% vs. 59%;
p>0.05). However, a significant increase in P-GSK3β-Ser9 expression was observed from dysplasias to carcinomas in Gal3+/+ mice (63% vs.
74%; p=0.01). In conclusion, these findings suggest that fully malignant transformation of the tongue epithelium is associated with increased P-
GSK3β-Ser9 expression in Gal3+/+ mice, but not in Gal3-/- mice. (IJCEP1203005).

Keywords: Oral carcinogenesis, immunohistochemistry, galectin-3, P-GSK3β-Ser9, tongue, mice


Address all correspondence to:
Dr. Paulo Rogério de Faria
Universidade Federal de Uberlândia
Instituto de Ciências Biomédicas
Avenida Pará 1720, Bloco 2B
Laboratório de Histologia, sala 2B-256
CEP: 38405-320, Uberlândia-MG, Brazil.
Tel: +55 34 3218-2240; Fax: +55 34 3218-2430
E-mail: paulorfaria@icbim.ufu.br