Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells.
Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells.
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DOI：
10.1186/1471-2407-10-391
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发表时间：
2010-07-23
期刊：
影响因子：
3.8
通讯作者：
Kim CW
中科院分区：
文献类型：
--
作者：
Jang JY;Jeon YK;Kim CW
在乳腺癌中，属于表皮生长因子受体家族的HER 2/neu癌蛋白可能触发磷酸肌醇-3激酶（PI 3 K）/Akt通路的激活，该通路控制细胞增殖、存活、迁移和侵袭。在这项研究中，我们研究了腺嘌呤核苷酸移位酶2（ANT 2）短发夹RNA（shRNA）介导的HER 2/neu下调和对PI 3 K/Akt信号通路的抑制作用是否抑制乳腺癌细胞的迁移和侵袭的问题。我们利用基于ANT 2载体的RNA干扰方法来抑制ANT 2表达，并且在整个研究中使用HER 2/neu过表达的人乳腺癌细胞系SK-BR 3。在这项研究中，ANT 2 shRNA通过促进HER 2/neu蛋白与热休克蛋白90（HSP 90）解离而降解，从而降低HER 2/neu蛋白水平。结果表明，ANT 2 shRNA对PI 3 K/Akt信号通路有抑制作用。通过抑制PI 3 K/Akt信号通路，可下调膜型基质金属蛋白酶1（MT 1-MMP）和血管内皮生长因子（VEGF）的表达，降低基质金属蛋白酶2（MMP 2）和MMP 9的活性，抑制乳腺癌细胞的迁移和侵袭。这些结果表明，通过shRNA敲低ANT 2通过抑制HSP 90的功能下调HER 2/neu，并抑制PI 3 K/Akt信号通路，最终导致乳腺癌细胞的迁移和侵袭受到抑制。
In breast cancer, the HER2/neu oncoprotein, which belongs to the epidermal growth factor receptor family, may trigger activation of the phosphoinositide-3 kinase (PI3K)/Akt pathway, which controls cell proliferation, survival, migration, and invasion. In this study, we examined the question of whether or not adenine nucleotide translocase 2 (ANT2) short hairpin RNA (shRNA)-mediated down-regulation of HER2/neu and inhibitory effects on the PI3K/Akt signaling pathway suppressed migration and invasiveness of breast cancer cells. We utilized an ANT2 vector-based RNA interference approach to inhibition of ANT2 expression, and the HER2/neu-overexpressing human breast cancer cell line, SK-BR3, was used throughout the study. In this study, ANT2 shRNA decreased HER2/neu protein levels by promoting degradation of HER2/neu protein through dissociation from heat shock protein 90 (HSP90). As a result, ANT2 shRNA induced inhibitory effects on the PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling by ANT2 shRNA caused down-regulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) expression, decreased matrix metalloproteinase 2 (MMP2) and MMP9 activity, and suppressed migration and invasion of breast cancer cells. These results indicate that knock-down of ANT2 by shRNA down-regulates HER2/neu through suppression of HSP90's function and inhibits the PI3K/Akt signaling pathway, resulting ultimately in suppressed migration and invasion of breast cancer cells.
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影响因子：
45.3
作者：
Cobleigh, MA;Vogel, CL;Slamon, DJ
通讯作者：
Slamon, DJ
影响因子：
11.5
作者：
Ono, Mayumi;Kuwano, Michihiko
通讯作者：
Kuwano, Michihiko
DOI：
10.1186/bcr1857
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Jang JY;Choi Y;Jeon YK;Kim CW
通讯作者：
Kim CW
DOI：
10.1073/pnas.97.8.3884
发表时间：
2000-04-11
影响因子：
11.1
作者：
Fang, JM;Shing, Y;Moses, MA
通讯作者：
Moses, MA
影响因子：
56.9
作者：
SLAMON, DJ;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL