AXIN2 Polymorphisms, the β-Catenin Destruction Complex Expression Profile and Breast Cancer Susceptibility

Abstract

<b>Background:</b> The Wnt/β-catenin signaling pathway is an important regulator of cellular functions suchas proliferation, survival and cell adhesion. Wnt/β-catenin signaling is associated with tumor initiation andprogression; β-catenin mutations explain only 30% of aberrant signaling found in breast cancer, indicating thatother components and/or regulation of the Wnt/β-catenin pathway may be involved. <br/><b>Objective</b>: We evaluatedAXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of β-catenin destruction complexgenes in breast cancer patients. Materials and <br/><b>Methods</b>: We collected peripheral blood samples from 102 breastcancer and 102 healthy subjects. The identification of the genetic variation was performed using PCR-RFLPsand DNA sequencing. RT-qPCR was used to determine expression profiles. <br/><b>Results</b>: We found significantassociation of AXIN2 rs151279728 and rs2240308 polymorphisms with breast cancer risk. Significant increasewas observed in AXIN2 level expression in breast cancer patients. Further analyses showed APC, β-catenin,CK1α, GSK3β and PP2A gene expression to be associated to clinic-pathological characteristics. <br/><b>Conclusions</b>:The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of β-catenindestruction complex expression may be found in breast cancer patients, providing additional support for rolesof Wnt/β-catenin pathway dysfunction in breast cancer tumorigenesis. However, the functional consequencesof the genetic alterations remain to be determined.