ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells


Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup withinthe armadillo (ARM) family, which has one or two ARM repeat domains as opposed to more than six-thirteenrepeats in the classical Armadillo family members. Materials and
Methods: In the study, we explore the biologicalfunctions of ALEX1 in breast cancer cells. Overexpression of ALEX1 and silencing of ALEX1 were performedwith 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 cellsinhibited proliferation and induced apoptosis. Furthermore, depletion of ALEX1 in MCF-7 breast cancer cellsincreased proliferation and inhibited apoptosis. Additional analyses demonstrated that the overexpression ofALEX1 activated the intrinsic apoptosis cascades through up-regulating the expression of Bax, cytosol cytochromec, 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 expressionof Bax, cytosol cytochrome c, active caspase-9, and active caspase-3 and up-regulating the level of Bcl-2 andmitochondria cytochrome c.
Conclusions: Our data suggest that ALEX1 as a crucial tumor suppressor genehas been involved in cell proliferation and apoptosis in breast cancer, which may serve as a novel candidatetherapeutic target.