ErbB2 down-regulates microRNA-205 in breast cancer
ErbB2 down-regulates microRNA-205 in breast cancer
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DOI：
10.1016/j.bbrc.2011.07.033
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发表时间：
2011-08-12
影响因子：
3.1
通讯作者：
Sakamaki, Toshiyuki
中科院分区：
文献类型：
--
作者：
Adachi, Ryohei;Horiuchi, Shota;Sakamaki, Toshiyuki
在大约20-30%的乳腺癌中观察到erbB 2（Her 2/neu）的基因扩增和蛋白质过表达。ErbB 2阳性乳腺癌比其他类型的乳腺癌更具侵袭性，因此需要进一步研究ErbB 2的信号通路以作为乳腺癌治疗的靶点。在这里，我们报告了microRNA-205（miR-205），一种也被报道与乳腺癌相关的分子，受到erbB 2过表达的负调控。乳腺上皮细胞外源性过表达erbB 2降低miR-205的表达，而增加细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶2（CDK 2）、细胞周期蛋白依赖性激酶4（CDK 4）和细胞周期蛋白依赖性激酶6（CDK 6）的表达。通过将erbB 2 siRNA转染到erbB 2过表达的乳腺癌上皮细胞中，降低的miR-205表达略有增加。erbB 2过表达可使乳腺上皮细胞在软琼脂中不依赖贴壁生长，而miR-205前体转染可降低乳腺上皮细胞在软琼脂中的生长能力。这些结果表明，在erbB 2过表达的乳腺上皮细胞中下调miR-205是erbB 2诱导的肿瘤发生所必需的，并且miR-205可能成为erbB 2阳性乳腺癌的新的重要替代治疗靶点。(C)2011 Elsevier Inc. All rights reserved.
Gene amplification and protein overexpression of erbB2 (Her2/neu) has been observed in approximately 20-30% of breast cancers. ErbB2-positive breast cancer is tend to be more aggressive than other types of breast cancer and therefore further investigation on the signaling pathways of erbB2 is needed for the therapeutic target for breast cancer treatment. Here we report that microRNA-205 (miR-205), a molecule also reported to be associated with breast cancer, is negatively regulated by erbB2 overexpression. Breast epithelial cells exogenously overexpressed with erbB2 decreased the expression of miR-205, whereas increased the expression of cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6). The decreased expression of miR-205 slightly increased by the transfection of erbB2 siRNA into the erbB2-overexpressing breast cancer epithelial cells. Overexpression of erbB2 enabled breast epithelial cells to grow anchorage-independently in soft agar, and the transfection of the precursor of miR-205 into the cells leaded to the decrease in the ability to grow in soft agar. These results suggest that down-regulation of miR-205 in erbB2-overexpressing breast epithelial cells is essential for erbB2-induced tumorigenesis, and miR-205 may have the potential to be a novel important alternative therapeutic target for erbB2-positive breast cancer. (C) 2011 Elsevier Inc. All rights reserved.