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

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

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자료유형: 학술저널

저자정보: 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)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제16호

발행연도: 2015.1

수록면: 7,277 - 7,284 (8page)

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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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