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

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)547-554
Number of pages8
JournalInternational Journal of Clinical and Experimental Pathology
Volume5
Issue number6
StatePublished - 2012

Keywords

  • Galectin-3
  • Immunohistochemistry
  • Mice
  • Oral carcinogenesis
  • P-GSK3β-Ser9
  • Tongue

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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