Β-catenin-LEF/TCF expression and roles in oral tissues and diseases

Alteration of the Wnt-signaling pathway is a major etiological factor for cancer and diseases affecting mineralized tissue development. Β-catenin is the key mediator of the Wnt pathway and alterations of its expression can cause dramatic changes in cell behavior. Β-catenin actions are mediated by its association with a family of transcription factors, named Lymphoid Enhancer Factor/T-Cell Factor (LEF/TCF). Data implicating β-catenin-LEF/TCF complexes in regulation of targets genes critical for normal development has been recently reported. Nevertheless, little is known about the distribution and potential roles of β-catenin-LEF/TCF in craniofacial tissues. Objectives: The aim of this study is (1) to characterize the expression of β-catenin-LEF/TCF in craniofacial cells; and (2) to investigate β-catenin-LEF/TCF mechanisms of action and the prognostic/diagnostic value of their expression in oral and craniofacial diseases. Methods: Β-catenin-LEF/TCF mRNA and protein expression was investigated in normal and pathological cell lines of oral epithelium, dental and bone tissues by RT-PCR, western-blot and immunohistochemistry. Β-catenin-LEF/TCF expression was then statistically correlated with the Wnt-signaling activity, proliferation rates, apoptotic index, and adhesion properties of each cell line. Results: Our data provide evidence that β-catenin-LEF/TCFs are differentially expressed in craniofacial tissue cell lines. Cells expressing high levels of nuclear β-catenin-LEF/TCF show enhanced Wnt-signaling activity, higher proliferation rates and diminished adhesion properties than cells expressing low/undetectable β-catenin-LEF/TCF. These features were dependent on specific combinations of β-catenin-LEF/TCF proteins and clearly correlated with the phenotype of each cell type. Conclusion: Taken together, our data suggest that β-catenin-LEF/TCF differential expression may play important roles with regard to cell behavior and may be used to predict disease outcome. Functional and translational studies (using pathological specimens) are being undertaken to further elucidate β-catenin-LEF/TCF roles in oral tissues. The information obtained will provide foundation for developing new diagnostic/prognostic tools and designing novel therapeutic modalities, resulting in improvement of oral health.