Survivin expression is regulated by coexpression of human epidermal growth factor receptor 2 and epidermal growth factor receptor via phosphatidylinositol 3-kinase/AKT signaling pathway in breast cancer cells
Survivin expression is regulated by coexpression of human epidermal growth factor receptor 2 and epidermal growth factor receptor via phosphatidylinositol 3-kinase/AKT signaling pathway in breast cancer cells
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DOI：
10.1158/0008-5472.can-05-0491
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发表时间：
2005-12-01
期刊：
影响因子：
11.2
通讯作者：
Sato, N
中科院分区：
文献类型：
--
作者：
Asanuma, H;Torigoe, T;Sato, N
Survivin是凋亡抑制蛋白家族的成员，广泛表达于多种人类癌组织中。生存素抑制半胱天冬酶的激活，其过度表达可导致对细胞凋亡刺激的抵抗。在这项研究中，通过免疫组织化学染色评估了 195 例浸润性乳腺癌标本的生存素蛋白表达。总体而言，79.5% 的肿瘤生存素呈阳性。还检测了53例表皮生长因子受体（EGFR）家族、人表皮生长因子受体2（HER2）和EGFR的表达，结果表明survivin阳性可能与HER2和EGFR的共表达相关。为了阐明乳腺癌细胞中生存素表达的调节机制，检查了HER2和/或EGFR表达对生存素水平的影响。研究表明，HER2和EGFR共表达可上调survivin蛋白水平，从而增强乳腺癌细胞对依托泊苷诱导的细胞凋亡的抵抗力。相反，当细胞用 HER2 特异性抑制剂赫赛汀处理时，生存素水平和细胞凋亡抵抗力降低。尽管赫赛汀可以下调 HER2 阳性乳腺癌细胞中的磷脂酰肌醇 3 激酶 (PI3K)/AKT 信号和丝裂原激活蛋白/细胞外信号相关激酶 (ERK) 激酶 1 (MEKI)/ERK 信号，但 PI3K 特异性抑制剂而非 MEK1 特异性抑制剂可以降低生存素水平。本研究阐明了HER2对乳腺癌细胞survivin蛋白表达的调控机制。
Survivin, a member of the inhibitor of apoptosis protein family, is widely expressed in a variety of human cancer tissues. Survivin inhibits activation of caspases, and its overexpression can lead to resistance to apoptotic stimuli. In this study, survivin protein expression was assessed by immunohistochemical staining of 195 invasive breast cancer specimens. Overall, 79.5% of the tumors were positive for survivin. The expression of epidermal growth factor receptor (EGFR) family, human epidermal growth factor receptor 2 (HER2) and EGFR, was also examined in 53 cases, and consequently, it was indicated that survivin positivity might be correlated with the coexpression of HER2 and EGFR. To clarify the regulatory mechanism of survivin expression in breast cancer cells, the effect of HER2 and/or EGFR expression on the survivin levels was examined. It was revealed that the survivin protein level was up-regulated by the coexpression of HER2 and EGFR, leading to the increased resistance against etoposide-induced apoptosis in breast cancer cells. Conversely, survivin levels and apoptosis resistance were decreased when cells were treated with HER2-specific inhibitor, Herceptin. Although Herceptin could down-regulate both phosphatidylinositol 3-kinase (PI3K)/AKT signal and mitogen-activated protein/extracellular signal-related kinase (ERK) kinase 1 (MEKI)/ERK signal in HER2-positive breast cancer cells, PI3K-specific inhibitor but not MEK1-specific inhibitor could decrease the survivin levels. The present study clarified the regulatory mechanism of HER2 in the expression of survivin protein in breast cancer cells.
DOI：
10.1111/j.1349-7006.1989.tb01693.x
发表时间：
1989-07
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Sato T;Okubo M;Wada Y;Sato N;Kikuchi K
通讯作者：
Kikuchi K