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

  • Aristizabal-Pachon, Andres Felipe (Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo) ;
  • Carvalho, Thais Inacio (Department of Oncology, Hospital Santa Casa of Ribeirao Preto) ;
  • Carrara, Helio Humberto (Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo) ;
  • Andrade, Jurandyr (Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo) ;
  • Takahashi, Catarina Satie (Department of Genetics, Ribeirao Preto Medical School, University of Sao Paulo)
  • Published : 2015.11.04


Background: The Wnt/${\beta}$-catenin signaling pathway is an important regulator of cellular functions such as proliferation, survival and cell adhesion. Wnt/${\beta}$-catenin signaling is associated with tumor initiation and progression; ${\beta}$-catenin mutations explain only 30% of aberrant signaling found in breast cancer, indicating that other components and/or regulation of the Wnt/${\beta}$-catenin pathway may be involved. Objective: We evaluated AXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of ${\beta}$-catenin destruction complex genes in breast cancer patients. Materials and Methods: We collected peripheral blood samples from 102 breast cancer and 102 healthy subjects. The identification of the genetic variation was performed using PCR-RFLPs and DNA sequencing. RT-qPCR was used to determine expression profiles. Results: We found significant association of AXIN2 rs151279728 and rs2240308 polymorphisms with breast cancer risk. Significant increase was observed in AXIN2 level expression in breast cancer patients. Further analyses showed APC, ${\beta}$-catenin, CK1${\alpha}$, GSK3${\beta}$ and PP2A gene expression to be associated to clinic-pathological characteristics. Conclusions: The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of ${\beta}$-catenin destruction complex expression may be found in breast cancer patients, providing additional support for roles of Wnt/${\beta}$-catenin pathway dysfunction in breast cancer tumorigenesis. However, the functional consequences of the genetic alterations remain to be determined.


AXIN2;beta-catenin destruction complex;breast cancer;SNP;RFLP-PCR;gene expression;RT-qPCR


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