Title : BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance.

Pub. Date : 2006 May

PMID : 16639080






7 Functional Relationships(s)
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1 BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance. Paclitaxel BRCA1 DNA repair associated Homo sapiens
2 In this report, we studied BRCA1 contribution to paclitaxel response in MCF-7 breast cancer cells. Paclitaxel BRCA1 DNA repair associated Homo sapiens
3 We show that MCF-7 cells transfected with BRCA1 siRNA display a significant increase in resistance to paclitaxel compared with the control cells. Paclitaxel BRCA1 DNA repair associated Homo sapiens
4 We next demonstrate that downregulation of BRCA1 reduces the mitotic index and triggers premature cyclin B1 degradation and decrease in Cdk1 activity following paclitaxel treatment, suggesting that BRCA1 downregulation results in precocious inactivation of the spindle checkpoint. Paclitaxel BRCA1 DNA repair associated Homo sapiens
5 We next demonstrate that downregulation of BRCA1 reduces the mitotic index and triggers premature cyclin B1 degradation and decrease in Cdk1 activity following paclitaxel treatment, suggesting that BRCA1 downregulation results in precocious inactivation of the spindle checkpoint. Paclitaxel BRCA1 DNA repair associated Homo sapiens
6 Furthermore, we show that BRCA1 up-regulates the expression of the protein kinase BubR1, essential component of the functional spindle checkpoint, whose downregulation is known to result in paclitaxel resistance in MCF-7 cells. Paclitaxel BRCA1 DNA repair associated Homo sapiens
7 Altogether, our findings support the notion that downregulation of BRCA1 expression mediates paclitaxel resistance through premature inactivation of spindle checkpoint in MCF-7 breast cancer cells. Paclitaxel BRCA1 DNA repair associated Homo sapiens