BRCA2蛋白对多倍体的抑制作用。

Suppression of polyploidy by the BRCA2 protein.

作者信息

Sagulenko Evgeny, Savelyeva Larissa, Ehemann Volker, Sagulenko Vitaliya, Hofmann Wera, Arnold Katrin, Claas Andreas, Scherneck Siegfried, Schwab Manfred

机构信息

Department of Tumor Genetics B030, German Cancer Research Centre, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

出版信息

Cancer Lett. 2007 Nov 8;257(1):65-72. doi: 10.1016/j.canlet.2007.07.003. Epub 2007 Aug 7.

DOI:10.1016/j.canlet.2007.07.003

PMID:17686574

Abstract

Mounting evidence implicates BRCA2 not only in maintenance of genome integrity but also in cell-cycle checkpoints. However, the contribution of BRCA2 in the checkpoints is still far from being understood. Here, we demonstrate that breast cancer cells MX-1 are unable to maintain genome integrity, which results in gross polyploidization. We generated MX-1 clones, stably expressing BRCA2, and found that BRCA2 acts to suppress polyploidy. Compared with MX-1, the ectopically BRCA2-expressing cells had different intracellular levels of Aurora A, Aurora B, p21, E2F-1, and pRb, suggesting a BRCA2-mediated suppression of polyploidy via stabilization of the checkpoint proteins levels.

摘要

越来越多的证据表明，BRCA2不仅参与基因组完整性的维持，还参与细胞周期检查点。然而，BRCA2在检查点中的作用仍远未被理解。在这里，我们证明乳腺癌细胞MX-1无法维持基因组完整性，这导致了严重的多倍体化。我们生成了稳定表达BRCA2的MX-1克隆，发现BRCA2起到抑制多倍体的作用。与MX-1相比，异位表达BRCA2的细胞中极光激酶A、极光激酶B、p21、E2F-1和磷酸化视网膜母细胞瘤蛋白的细胞内水平不同，这表明BRCA2通过稳定检查点蛋白水平介导对多倍体的抑制。