Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression.
Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression.
复制标题
细胞周期蛋白 D3 可以补偿 ErbB2 诱导的乳腺肿瘤发生和进展过程中细胞周期蛋白 D1 的损失。
DOI：
10.1158/0008-5472.can-11-1783
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发表时间：
2011
期刊：
影响因子：
11.2
通讯作者：
Wagner,Kay-Uwe
中科院分区：
文献类型：
--
作者：
Zhang,Qian;Sakamoto,Kazuhito;Liu,Chengbao;Triplett,AleataA;Lin,Wan-chi;Rui,Hallgeir;Wagner,Kay-Uwe
Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferationin vitroand decreased the tumor burdenin vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy.Cancer Res; 71(24); 7513–24. ©2011 AACR.
