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ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells

  • Gao, Yue (Molecular Medicine & Cancer Research Center, Chongqing Medical University) ;
  • Wu, Jia-Yan (Molecular Medicine & Cancer Research Center, Chongqing Medical University) ;
  • Zeng, Fan (Molecular Medicine & Cancer Research Center, Chongqing Medical University) ;
  • Liu, Ge-Li (Molecular Medicine & Cancer Research Center, Chongqing Medical University) ;
  • Zhang, Han-Tao (Molecular Medicine & Cancer Research Center, Chongqing Medical University) ;
  • Yun, Hong (Foreign Language College, Chongqing Medical University) ;
  • Song, Fang-Zhou (Molecular Medicine & Cancer Research Center, Chongqing Medical University)
  • Published : 2015.04.29

Abstract

Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo (ARM) family, which has one or two ARM repeat domains as opposed to more than six-thirteen repeats in the classical Armadillo family members. Materials and Methods: In the study, we explore the biological functions of ALEX1 in breast cancer cells. Overexpression of ALEX1 and silencing of ALEX1 were performed with SK-BR3 and MCF-7 cell lines. Cell proliferation and colony formation assays, along with flow cytometry, were carried out to evaluate the roles of ALEX1. Results: ALEX1 overexpression in SK-BR3 breast cancer cells inhibited proliferation and induced apoptosis. Furthermore, depletion of ALEX1 in MCF-7 breast cancer cells increased proliferation and inhibited apoptosis. Additional analyses demonstrated that the overexpression of ALEX1 activated the intrinsic apoptosis cascades through up-regulating the expression of Bax, cytosol cytochrome c, active caspase-9 and active caspase-3 and down-regulating the levels of Bcl-2 and mitochondria cytochrome c. Simultaneouly, silencing of ALEX1 inhibited intrinsic apoptosis cascades through down-regulating the expression of Bax, cytosol cytochrome c, active caspase-9, and active caspase-3 and up-regulating the level of Bcl-2 and mitochondria cytochrome c. Conclusions: Our data suggest that ALEX1 as a crucial tumor suppressor gene has been involved in cell proliferation and apoptosis in breast cancer, which may serve as a novel candidate therapeutic target.

Keywords

Breast cancer;ALEX1;cell proliferation;apoptosis;active caspase-3

Acknowledgement

Supported by : Ministry of Education of China

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