Identification of tumor-initiating cells in a p53-null mouse model of breast cancer
Identification of tumor-initiating cells in a p53-null mouse model of breast cancer
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DOI：
10.1158/0008-5472.can-07-6353
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发表时间：
2008-06-15
期刊：
影响因子：
11.2
通讯作者：
Rosen, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Zhang, Mei;Behbod, Fariba;Rosen, Jeffrey M.
我们利用与人乳腺癌相似的同基因p53缺失小鼠乳腺肿瘤模型，通过有限稀释移植和体外乳腺球试验，鉴定了肿瘤起始细胞的Lin（-）CD 29（H）CD 24（H）亚群。在随后的移植中，该亚群产生了显示出与原发性肿瘤相似性质的异质性肿瘤。生物标志物的分析表明，Lin-CD 29（H）CD 24（H）亚群可能来自双能乳腺祖细胞。Lin（-）CD 29（H）CD 24（H）小鼠乳腺肿瘤起始细胞群中差异表达的基因包括参与DNA损伤反应和修复的基因，以及参与表观遗传调控的基因，这些基因先前被证明对干细胞自我更新至关重要。这些研究提供了支持癌症干细胞（CSC）假说的体外和体内数据。此外，这种p53基因缺失的小鼠乳腺肿瘤模型可能使我们能够识别新的CSC标志物，并测试这些标志物的功能重要性。
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin-CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. Furthermore, this p53-null mouse mammary tumor model may allow us to identify new CSC markers and to test the functional importance of these markers.