BRCA1 regulates gene expression for orderly mitotic progression
BRCA1 regulates gene expression for orderly mitotic progression
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DOI：
10.4161/cc.4.11.2152
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发表时间：
2005-11-01
期刊：
影响因子：
4.3
通讯作者：
Rosen, EM
中科院分区：
文献类型：
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作者：
Bae, I;Rih, JK;Rosen, EM
BRCA1基因的种系突变会增加患乳腺癌和卵巢癌的风险。为了研究BRCA1对散发性癌症（通常表现为BRCA1表达降低）的贡献，我们测试了敲低BRCA1对人前列腺（DU-145）和乳腺癌（MCF-7）癌细胞基因表达的影响。DNA微阵列和验证性RNA分析显示，BRCA1小干扰（si） RNA导致与有丝分裂纺锤体检查点相关的多个基因下调(例如。， BUB1B， HEC和STK6)，染色体分离(如；， ESPL1， NEK2和PTTG1)，中心体功能(例如；（如ASPM），细胞质分裂(如；PRC1， PLK和KNSL2)，以及进入和通过有丝分裂的进展(例如。CDC2和CDC20)。用BRCA1-siRNA处理的细胞显示有丝分裂纺锤体检查点的衰减；但不是几个G2检查站。最后，BRCA1敲低导致多核细胞积聚，提示细胞分裂存在缺陷。我们得出结论，BRCA1调控有序有丝分裂过程的基因表达。
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.