EZH2 knockdown suppresses the growth and invasion of human inflammatory breast cancer cells.
EZH2 knockdown suppresses the growth and invasion of human inflammatory breast cancer cells.
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EZH2敲低抑制了人类炎症性乳腺癌细胞的生长和侵袭。
DOI：
10.1186/1756-9966-32-70
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发表时间：
2013-09-27
期刊：
影响因子：
--
通讯作者：
Cristofanilli M
中科院分区：
文献类型：
--
作者：
Mu Z;Li H;Fernandez SV;Alpaugh KR;Zhang R;Cristofanilli M
炎症性乳腺癌（IBC）是所有类型乳腺癌患者中最易转移的乳腺癌变体，生存率最低，目前IBC的治疗靶点非常有限。zeste同源物增强子2 （Enhancer of zeste homolog 2, EZH2）在人IBC中频繁表达，其表达与较差的临床预后呈正相关。然而，EZH2促进IBC的分子基础尚未探索。在这里，我们通过检测EZH2敲除对体外和体内原位异种移植模型中肿瘤球体形成和这些细胞侵袭的影响，研究了EZH2在IBC细胞中的功能作用。本研究使用了SUM149和一种新的IBC细胞系fc -IBC-02，该细胞系来源于IBC患者的胸腔积液。使用人类EZH2基因特异性短发夹RNA （shRNA）进行EZH2的特异性敲除。体外观察细胞的生长和肿瘤球体的形成。用Boyden室法检测EZH2基因敲低对IBC细胞迁移和侵袭的影响。在体内肿瘤生长研究中，IBC细胞被原位移植到免疫缺陷小鼠的乳腺脂肪垫中。结果表明，与正常乳腺上皮细胞相比，EZH2在人IBC细胞系中的表达水平较高，下调EZH2的表达可显著抑制体外IBC细胞的生长和肿瘤球体的形成。此外，EZH2敲低可抑制IBC细胞的迁移和侵袭。EZH2敲低显著抑制IBC细胞的血管生成和肿瘤生长。我们的研究结果提供了直接证据，证明EZH2对肿瘤球体的形成和人类IBC细胞的侵袭至关重要，可能成为开发人类IBC新治疗策略的潜在靶点。
Inflammatory breast cancer (IBC) is the most metastatic variant of breast cancer with the poorest survival in all types of breast cancer patients and presently therapeutic targets for IBC are very limited. Enhancer of zeste homolog 2 (EZH2) is frequently expressed in human IBC and its expression positively correlates with worse clinical outcome. However, the molecular basis for EZH2 promoting IBC has not been explored. Here, we investigated the functional role of EZH2 in IBC cells by examining the effects of its knockdown on the formation of tumor spheroids and invasion of these cells in vitro and in vivo in an orthotopic xenograft model. SUM149 and a new IBC cell line-FC-IBC-02 derived from pleural effusion fluid of an IBC patient were used in this study. Specific knockdown of EZH2 was performed using short hairpin RNA (shRNA) specific to the human EZH2 gene. Cell growth and the formation of tumor spheroids were examined in vitro. The effects of EZH2 knockdown on IBC cell migration and invasion were examined by a Boyden chamber assay. For the in vivo tumor growth studies, IBC cells were orthotopically transplanted into the mammary fat pads of immunodeficient mice. The results showed that EZH2 is expressed at higher levels in human IBC cell lines compared with normal human mammary epithelial cells, and the knockdown of EZH2 expression significantly suppressed cell growth and tumor spheroid formation of human IBC cells in vitro. In addition, EZH2 knockdown inhibited the migration and invasion of IBC cells. Significantly, EZH2 knockdown suppressed the angiogenesis and tumor growth of IBC cells in vivo. Our results provide direct evidence that EZH2 is critical for the formation of tumor spheroids and invasion of human IBC cells and could be a potential target for developing novel therapeutic strategies for human IBC.
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影响因子：
6.6
作者：
Holm, Karolina;Grabau, Dorthe;Ringner, Markus
通讯作者：
Ringner, Markus
EZH2的下调降低了雌激素受体阴性侵入性乳腺癌的生长，需要BRCA1。
影响因子：
8
作者：
Gonzalez, M. E.;Li, X.;Toy, K.;DuPrie, M.;Ventura, A. C.;Banerjee, M.;Ljungman, M.;Merajver, S. D.;Kleer, C. G.
通讯作者：
Kleer, C. G.
DOI：
10.1158/1541-7786.mcr-10-0398
发表时间：
2010-12
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Li H;Cai Q;Godwin AK;Zhang R
通讯作者：
Zhang R
影响因子：
50.3
作者：
Chang CJ;Yang JY;Xia W;Chen CT;Xie X;Chao CH;Woodward WA;Hsu JM;Hortobagyi GN;Hung MC
通讯作者：
Hung MC
影响因子：
4.3
作者：
Amatangelo, Michael D.;Garipov, Azat;Zhang, Rugang
通讯作者：
Zhang, Rugang