Abstract
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. GSK3β gene is an important Wnt signaling regulator involved in β-Catenin degradation. Wnt signaling is associated with initiation and progression process in many tumor types, and alterations in β-Catenin explain only a small proportion of aberrant signaling found in breast cancer, indicating that other Wnt signaling components and/or regulators as GSK3β may be involved.
OBJECTIVE:
The aim of this study was to evaluate the genetic, epigenetic and transcriptional alterations of GSK3β 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 GSK3β expression levels.
RESULTS:
The rs334558 polymorphism showed a strong association with aggressive cancer. A significant increase was observed in GSK3β expression level respect to hormone receptors status and tumor size.
CONCLUSION:
The results indicated an inverse relationship between GSK3β performance and tumor progression. This is the first study to relate GSK3β gene with breast cancer in Brazilian population.
Keywords: rs334558, wnt signaling, β-catenin destruction complex, PCR-RFPLs, RT-qPCR
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