BRCA1 regulates gene expression for orderly mitotic progression

被引：56

作者：

Bae, I ^{[1
]}

Rih, JK ^{[1
]}

Kim, HJ ^{[1
]}

Kang, HJ ^{[1
]}

Haddad, B ^{[1
]}

Kirilyuk, A ^{[1
]}

Fan, SJ ^{[1
]}

Avantaggiati, ML ^{[1
]}

Rosen, EM ^{[1
]}

机构：

[1] Georgetown Univ, Dept Oncol, Lombardi Canc Ctr, Washington, DC 20057 USA

来源：

CELL CYCLE | 2005年 / 4卷 / 11期

关键词：

breast cancer susceptibility gene-1 (BRCA1); gene expression; microarray; DU-145; MCF-7; MDA-MB-231; mitotic spindle checkpoint; spindle assembly checkpoint;

D O I：

10.4161/cc.4.11.2152

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Germline mutations of the BRCA1 gene confer an increased risk for breast cancer and ovarian cancer. To study the contribution of BRCA1 to sporadic cancers, which often exhibit reduced BRCA1 expression, we tested the effect of knocking down BRCA1 on gene expression in human prostate (DU-145) and breast (MCF-7) cancer cells. DNA microarray and confirmatory RNA analyses revealed that BRCA1 small interfering ( si) RNA caused down-regulation of multiple genes implicated in the mitotic spindle checkpoint (eg., BUB1B, HEC, and STK6), chromosome segregation ( eg., ESPL1, NEK2, and PTTG1), centrosome function ( eg., ASPM), cytokinesis ( eg., PRC1, PLK, and KNSL2), and the progression into and through mitosis ( eg., CDC2, and CDC20). Cells treated with BRCA1-siRNA showed attenuation of the mitotic spindle checkpoint; but not several G2 checkpoints. Finally, BRCA1 knockdown caused the accumulation of multinucleated cells, suggesting a defect in cytokinesis. We conclude that BRCA1 regulates gene expression for orderly mitotic progression.

引用

页码：1641 / 1666

页数：26

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