Estudo da expressão de proteínas da via Wnt e Hedgehog na carcinogênese bucal em camundongos wild-type e knockout para o gene da galectina-3

Abstract

Squamous cell carcinoma (SCC) is the most common neoplasm of the oral cavity and each year more than 300.000 new cases are diagnosed worldwide. To understand the molecular alterations associated with its development as well as to identify diagnostic and prognostic markers for this tumor, lots of studies have used mouse model of oral carcinogenesis challenged with the carcinogen 4-Nitroquinoline-1-Oxide (4NQO). Galectin-3 (Gal-3) is a lectin that has the hability to modulate intracellular signaling pathways, such as the Wnt/β-catenin pathway. Furthermore, the Wnt/β-catenin- regulated protein GSK-3β is able to control cytoplasmic level of β-catenin and also inactivate effector proteins of the Hedgehog (Hh) signaling pathway including Gli proteins. The aim of this study was evaluate by immunohistochemistry Wnt-1 and Wnt-3A expression, both responsible to activate the Wnt/ β-catenin pathway, and Shh and Gli-3 expression, two proteins belonging to the Hh signaling pathway, in samples of dysplasia and carcinomas developed in tongue from wild-type (WT) and Gal-3-knockout (KO) mice challenged by the carcinogen 4NQO. To analyze the expression of these proteins, a semiquantitative method was employed. All samples of dysplasia and carcinoma were negative for Wnt-1 protein in both groups of mice. The average of positivity for Wnt-3A protein was higher in the WT group, but no difference was found between the two groups (p=0,04). Shh expression was always statistically significant in the WT group when compared to the KO group both in dysplasia as carcinoma (p<0.0001). Furthermore, Shh expression was associated with malignant transformation of tongue epithelium only in the WT group. With regard to Gli-3 protein, its expression decreased from dysplasia to carcinoma in the WT group, whereas in the KO group it was observed a slight increased, but no difference was achieved. In conclusion, the results suggest that absence of Gal-3 does not interfere in the Wnt/β-catenin signaling pathway activation. Also, the Hh signaling pathway plays an important role in the malignant transformation of tongue epithelium from WT mice, but not in KO mice.