Role of GSK3ß in breast cancer susceptibility.

BACKGROUND: Breast cancer is one of the principal causes of death among Brazilian women, so it is a challenge to find new and specific early diagnostic markers, using simple and fast procedures. GSK3ß gene is an important Wnt signaling regulator involved in ß-Catenin degradation. Wnt signaling is associated with initiation and progression process in many tumor types, and alterations in ß-Catenin explain only a small proportion of aberrant signaling found in breast cancer, indicating that other Wnt signaling components and/or regulators as GSK3ß may be involved. OBJECTIVE: The aim of this study was to evaluate the genetic, epigenetic and transcriptional alterations of GSK3ß in breast cancer. METHODS: Peripheral blood samples from 204 breast cancer and healthy women were collected. Assessment of rs334558 polymorphism was performed by PCR-RFLP, promoter methylation profiles analysis by MS-PCR and qPCR was used to determine GSK3ß expression levels. RESULTS: The rs334558 polymorphism showed a strong association with aggressive cancer. A significant increase was observed in GSK3ß expression level respect to hormone receptors status and tumor size. CONCLUSION: The results indicated an inverse relationship between GSK3ß performance and tumor progression. This is the first study to relate GSK3ß gene with breast cancer in Brazilian population.