Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer
Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer
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DOI：
10.1158/0008-5472.can-05-0712
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发表时间：
2005-12-01
期刊：
影响因子：
11.2
通讯作者：
Raman, V
中科院分区：
文献类型：
--
作者：
Mironchik, Y;Winnard, PT;Raman, V
侵袭性癌症表型是许多不同基因改变的表现，这些改变促进快速增殖和转移。在这项研究中，我们证明 Twist 在乳腺癌细胞系 MCF-7 中的稳定过度表达，将其形态改变为成纤维细胞样表型，表现出代表间充质转化的蛋白质标记。此外，观察到与空载体对照细胞相比，MCF-7/Twist 细胞的血管内皮生长因子 (VEGF) 合成增加。通过MCF-7/Twist异种移植肿瘤的功能磁共振成像（MRI）分析VEGF在体内诱导的功能变化。 MRI 显示 MCF-7/Twist 肿瘤在体内表现出比 MCF-7/载体对照异种移植物更高的血管体积和血管通透性。此外，从患者获得的乳腺肿瘤样本中 Twist 表达升高与高级别浸润性癌和染色体不稳定，特别是 1 号和 7 号染色体的增加密切相关。总之，这些结果表明，乳腺癌细胞中 Twist 过度表达可以诱导血管生成，与染色体不稳定性相关，并促进上皮-间质样转变，这对于转变为侵袭性乳腺癌表型至关重要。 （癌症研究 2005 年；65(23)：10801-9）。
Aggressive cancer phenotypes are a manifestation of many different genetic alterations that promote rapid proliferation and metastasis. In this study, we show that stable overexpression of Twist in a breast cancer cell line, MCF-7, altered its morphology to a fibroblastic-like phenotype, which exhibited protein markers representative of a mesenchymal transformation. In addition, it was observed that MCF-7/Twist cells had increased vascular endothelial growth factor (VEGF) synthesis when compared with empty vector control cells. The functional changes induced by VEGF in vivo were analyzed by functional magnetic resonance imaging (MRI) of MCF-7/Twist-xenografted tumors. MRI showed that MCF-7/Twist tumors exhibited higher vascular volume and vascular permeability in vivo than the MCF-7/vector control xenografts. Moreover, elevated expression of Twist in breast tumor samples obtained from patients correlated strongly with high-grade invasive carcinomas and with chromosome instability, particularly gains of chromosomes 1 and 7. Taken together, these results show that Twist overexpression in breast cancer cells can induce angiogenesis, correlates with chromosomal instability, and promotes an epithelial-mesenchymal-like transition that is pivotal for the transformation into an aggressive breast cancer phenotype. (Cancer Res 2005; 65(23): 10801-9).