Andrés Felipe Aristizabal-Pachon1,2, Willian Orlando Castillo1. 1. Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 2. Center for Cell-Based Therapy, National Institute of Science and Technology in Stem Cell and Cell Therapy, Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil.
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.
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.
Authors: Andres Felipe Aristizabal-Pachon; Yeimy Gonzalez-Giraldo; Angela Yazmin Garcia; Dalia Xiomara Suarez; Angela Rodriguez; Janneth Gonzalez-Santos Journal: Asian Pac J Cancer Prev Date: 2022-01-01