BRCA1 regulates gene expression for orderly mitotic progression.
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.
Bae
Insoo
I
Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20057-1469, USA.
Rih
Jeong Keun
JK
Kim
Hee Jeong
HJ
Kang
Hyo Jin
HJ
Haddad
Bassem
B
Kirilyuk
Alexander
A
Fan
Saijun
S
Avantaggiati
Maria L
ML
Rosen
Eliot M
EM
D019313:BRCA1 Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D008938:Mitosis / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D019313:BRCA1 Protein