Overexpression of ΔNp63α induces a stem cell phenotype in MCF7 breast carcinoma cell line through the Notch pathway
Overexpression of ΔNp63α induces a stem cell phenotype in MCF7 breast carcinoma cell line through the Notch pathway
复制标题
DOI：
10.1111/j.1349-7006.2010.01700.x
复制
发表时间：
2010-11-01
期刊：
影响因子：
5.7
通讯作者：
Zhao, Robert Chunhua
中科院分区：
文献类型：
--
作者：
Du, Zhijian;Li, Jing;Zhao, Robert Chunhua
为了阐明 Delta Np63 α 在乳腺癌中的作用，使用免疫化学方法测定了 50 例临床乳腺癌标本中 p63、雌激素受体、孕激素受体、p53、CK5、cerBb-2 和 Notch1 的表达水平。 P63 在具有基底细胞样特征的乳腺癌子集中高表达。然后，我们用Delta Np63 α质粒转染MCF7细胞，并在转染后测定其癌症干细胞样特征。 MCF7 细胞中 Delta Np63 α 的过表达使 CD24-CD44+ 亚群的百分比从 2.2 +/- 0.2% 增加到 25.1 +/- 1.5% (P < 0.05)，并导致癌细胞增殖、克隆形成、贴壁依赖性生长和体内异种移植物发生率增加。此外，过度表达 Delta Np63 α 的癌细胞具有更强的耐药性。进一步的研究表明 Delta Np63 α 诱导的 Notch 通路激活可能在这些效应中发挥作用。染色质免疫沉淀证实 Delta Np63 α 可以直接与 Notch1 结合。在临床乳腺癌标本中，还发现p63的表达水平与Notch1的表达水平呈正相关。我们的结果表明 Delta Np63 α 可能作为乳腺癌中的肿瘤启动转录因子。 （癌症科学 2010 年；101：2417-2424）。
To elucidate a role of Delta Np63 alpha in breast cancer, the expression levels of p63, estrogen receptor, progesterone receptor, p53, CK5, cerBb-2, and Notch1 were assayed in 50 clinical breast cancer specimens using immunochemistry. P63 was highly expressed in a subset of breast cancer with basal-like features. We then transfected MCF7 cells with Delta Np63 alpha plasmid, and assayed its cancer stem cell-like features after transfection. Overexpression of Delta Np63 alpha in MCF7 cells increased the percentage of CD24-CD44+ subpopulation from 2.2 +/- 0.2% to 25.1 +/- 1.5% (P < 0.05) and led to increased cancer cell proliferation, clonogenicity, anchorage-independent growth, and the incidence of xenograft grown in vivo. In addition, Delta Np63 alpha overexpressing cancer cells were more drug resistant. Further studies suggested Delta Np63 alpha-induced activation of the Notch pathway may play a role in these effects. Chromatin immunoprecipitation confirmed that Delta Np63 alpha could directly bind to Notch1. In clinical breast cancer specimens, the expression level of p63 was also found to positively correlate with the expression level of Notch1. Our results suggest that Delta Np63 alpha might serve as a tumor initiating transcription factor in breast cancer. (Cancer Sci 2010; 101: 2417-2424).