GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model
GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model
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DOI：
10.1016/j.ccr.2008.01.011
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发表时间：
2008-02-01
期刊：
影响因子：
50.3
通讯作者：
Werb, Zena
中科院分区：
文献类型：
--
作者：
Kouros-Mehr, Hosein;Bechis, Seth K.;Werb, Zena
乳腺癌如何能够传播和转移知之甚少。使用增生移植系统，我们表明，在肿瘤进展过程中，肿瘤的传播和转移发生在离散的步骤。生物信息学分析显示，转录因子加塔-3的缺失标志着从腺瘤到早期癌的进展和肿瘤扩散的开始。晚期癌中加塔-3的恢复诱导肿瘤分化并抑制肿瘤扩散。在早期肿瘤中靶向缺失加塔-3导致分化细胞凋亡，表明其缺失不足以导致恶性转化。相反，恶性进展伴随着加塔-3阴性肿瘤细胞群的扩增而发生。这些数据表明，加塔-3调节乳腺癌中的肿瘤分化并抑制肿瘤扩散。
How breast cancers are able to disseminate and metastasize is poorly understood. Using a hyperplasia transplant system, we show that tumor dissemination and metastasis occur in discrete steps during tumor progression. Bioinformatic analysis revealed that loss of the transcription factor GATA-3 marked progression from adenoma to early carcinoma and onset of tumor dissemination. Restoration of GATA-3 in late carcinomas induced tumor differentiation and suppressed tumor dissemination. Targeted deletion of GATA-3 in early tumors led to apoptosis of differentiated cells, indicating that its loss is not sufficient for malignant conversion. Rather, malignant progression occurred with an expanding GATA-3-negative tumor cell population. These data indicate that GATA-3 regulates tumor differentiation and suppresses tumor dissemination in breast cancer.