BRCA1 regulates gene expression for orderly mitotic progression.
Cell Cycle
; 4(11): 1641-66, 2005 Nov.
Article
in En
| MEDLINE
| ID: mdl-16258266
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Neoplastic
/
BRCA1 Protein
/
Mitosis
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Cell Cycle
Year:
2005
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA