作者: Mei T. Lai , John L. Tonkinson , Jeffrey S. Larson
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摘要: Mutations in BRCA1 increase the risk of breast and ovarian cancer. Although mechanism by which mutant alters growth regulation is unknown, COOH terminus appears to play a critical role. To examine this, we introduced vector expressing COOH-terminal residues 1293–1863 (CT-BRCA1) into nontumorigenic human epithelial cells. Overexpression CT-BRCA1 led reduction doubling time (from 64 44 h) decreased reliance on factors, suggesting that this may function dominant-negative manner. Expression induced alterations cell cycle control, mainly G2-M, including loss G2-M block colchicine. These results suggest one BRCA1-related control occurs governing checkpoint(s) between DNA replication mitosis.