Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability.
Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability.
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DOI：
10.1186/1471-2407-8-286
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发表时间：
2008-10-04
期刊：
影响因子：
3.8
通讯作者：
Yoo BC
中科院分区：
文献类型：
--
作者：
Kang SH;Kang KW;Kim KH;Kwon B;Kim SK;Lee HY;Kong SY;Lee ES;Jang SG;Yoo BC
阐明肿瘤对赫赛汀耐药的分子机制对于治疗Her 2过表达的转移性乳腺癌至关重要。为了在分子水平上进一步了解赫赛汀耐药机制，我们使用比较蛋白质组学方法分析了两种人乳腺癌细胞系：Her 2阳性SK-BR-3细胞及其赫赛汀耐药SK-BR-3（SK-BR-3 HR）细胞。热休克蛋白27（HSP 27）的表达被证明是上调SK-BR-3 HR细胞。通过特异性siRNA转染抑制HSP 27增加了SK-BR-3 HR细胞对赫赛汀的敏感性。在赫赛汀的存在下，Her 2在两种细胞系中下调。然而，与SK-BR-3 HR细胞相比，SK-BR-3亲本细胞中Her 2表达降低的量更大。有趣的是，免疫共沉淀分析表明HSP 27可以与Her 2结合。在不存在赫赛汀的情况下，HSP 27表达被抑制，Her 2表达减少，表明Her 2-HSP 27复合物的形成可以阻碍Her 2通过赫赛汀的下调。我们目前的研究表明，在人乳腺癌细胞中上调的HSP 27可以通过增加Her 2蛋白的稳定性来降低Herceptin的敏感性。
Elucidating the molecular mechanisms by which tumors become resistant to Herceptin is critical for the treatment of Her2-overexpressed metastatic breast cancer. To further understand Herceptin resistance mechanisms at the molecular level, we used comparative proteome approaches to analyze two human breast cancer cell lines; Her2-positive SK-BR-3 cells and its Herceptin-resistant SK-BR-3 (SK-BR-3 HR) cells. Heat-shock protein 27 (HSP27) expression was shown to be upregulated in SK-BR-3 HR cells. Suppression of HSP27 by specific siRNA transfection increased the susceptibility of SK-BR-3 HR cells to Herceptin. In the presence of Herceptin, Her2 was downregulated in both cell lines. However, Her2 expression was reduced by a greater amount in SK-BR-3 parent cells than in SK-BR-3 HR cells. Interestingly, co-immunoprecipitation analysis showed that HSP27 can bind to Her2. In the absence of Herceptin, HSP27 expression is suppressed and Her2 expression is reduced, indicating that downregulation of Her2 by Herceptin can be obstructed by the formation of a Her2-HSP27 complex. Our present study demonstrates that upregulated HSP27 in human breast cancer cells can reduce Herceptin susceptibility by increasing Her2 protein stability.
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影响因子：
11.2
作者：
Shin, YK;Yoo, BC;Park, JG
通讯作者：
Park, JG
影响因子：
11.4
作者：
GrausPorta, D;Beerli, RR;Hynes, NE
通讯作者：
Hynes, NE
影响因子：
3.4
作者：
Li, Da-Qiang;Wang, Lei;Shao, Zhi-Min
通讯作者：
Shao, Zhi-Min
影响因子：
8.8
作者：
Conroy, S E;Sasieni, P D;Amin, V;Wang, D Y;Smith, P;Fentiman, I S;Latchman, D S
通讯作者：
Latchman, D S
影响因子：
9.7
作者：
Casado, Pedro;Zuazua-Villar, Pedro;Ramos, Sofia
通讯作者：
Ramos, Sofia