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

Andres Felipe Aristizabal-Pachon,Jurandyr Andrade,Catarina Satie Takahashi,Thais Inacio Carvalho,Helio Humberto Carrara

doi:10.7314/apjcp.2015.16.16.7277

Andres Felipe Aristizabal-Pachon, Jurandyr Andrade + Show 3 more

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https://doi.org/10.7314/apjcp.2015.16.16.7277

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Abstract

The Wnt/β-catenin signaling pathway is an important regulator of cellular functions such as proliferation, survival and cell adhesion. Wnt/β-catenin signaling is associated with tumor initiation and progression; β-catenin mutations explain only 30% of aberrant signaling found in breast cancer, indicating that other components and/or regulation of the Wnt/β-catenin pathway may be involved. We evaluated AXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of β-catenin destruction complex genes in breast cancer patients. 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. 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, β-catenin, CK1α, GSK3β and PP2A gene expression to be associated to clinic-pathological characteristics. The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of β-catenin destruction complex expression may be found in breast cancer patients, providing additional support for roles of Wnt/β-catenin pathway dysfunction in breast cancer tumorigenesis. However, the functional consequences of the genetic alterations remain to be determined.

Highlights

Breast cancer is one of the most common diseases suffered by women around the world, with an estimated 990,000 new cases and 375,000 deaths each year (Brito et al, 2009)
The Wnt pathway plays an important role in the carcinogenesis process, as part of proliferation, differentiation and cell morphogenesis processes; alterations of Wnt pathway have been linked to different cancers, including breast cancer (Howe and Brown, 2004; Polakis, 2007; Clevers and Nusse, 2012; Khalil et al, 2012)
Genetic alterations of Wnt pathway components were strongly associated with different pathologies and AXIN2 have been associated with dental agenesis (Lammi et al, 2004; Mostowska et al, 2006), orofacial clefts (Letra et al, 2009; Han et al, 2014) and cancer (Lustig et al, 2002; Salahshor and Woodgett, 2005; Gunes et al, 2009; Chapman et al, 2011; Alanazi et al, 2013)

Summary

Introduction

Breast cancer is one of the most common diseases suffered by women around the world, with an estimated 990,000 new cases and 375,000 deaths each year (Brito et al, 2009). Breast cancer is the main cause of death in women between 35 and 64 years old in Brazil and South America, new research efforts aimed at identifying mechanisms and developing tools for early disease detection; in this way, in recent years, many studies have shown that breast cancer is a heterogeneous disease, including a variety of molecular subgroups based on differential expression patterns (Alanazi et al, 2013). Objective: We evaluated AXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of β-catenin destruction complex genes in breast cancer patients. Conclusions: The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of β-catenin destruction complex expression may be found in breast cancer patients, providing additional support for roles of Wnt/β-catenin pathway dysfunction in breast cancer tumorigenesis. The functional consequences of the genetic alterations remain to be determined

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