ALEX1 Regulates Proliferation and Apoptosis in Breast Cancer Cells.
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.


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.
Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, China E-mail : fzsongcq@163.com.
Yue
Y
Gao
Jia-Yan
JY
Wu
Fan
F
Zeng
Ge-Li
GL
Liu
Han-Tao
HT
Zhang
Hong
H
Yun
Fang-Zhou
FZ
Song
D017209:Apoptosis / Q000235:genetics*; D051186:Armadillo Domain Proteins / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055879:Gene Knock-In Techniques; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C422103:ARMCX1 protein, human; D051186:Armadillo Domain Proteins; C494826:BAX protein, human; D015513:Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9