在管腔型乳腺癌模型中，GATA-3将肿瘤分化与扩散联系起来。
GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model.
作者信息
Kouros-Mehr Hosein, Bechis Seth K, Slorach Euan M, Littlepage Laurie E, Egeblad Mikala, Ewald Andrew J, Pai Sung-Yun, Ho I-Cheng, Werb Zena
机构信息
Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA.
出版信息
Cancer Cell. 2008 Feb;13(2):141-52. doi: 10.1016/j.ccr.2008.01.011.
Abstract
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.
摘要
乳腺癌如何扩散和转移目前尚不清楚。我们利用增生移植系统发现，肿瘤扩散和转移在肿瘤进展过程中是分阶段发生的。生物信息学分析表明，转录因子GATA-3的缺失标志着从腺瘤到早期癌的进展以及肿瘤扩散的开始。在晚期癌中恢复GATA-3可诱导肿瘤分化并抑制肿瘤扩散。在早期肿瘤中靶向缺失GATA-3会导致分化细胞凋亡，这表明其缺失不足以导致恶性转化。相反，恶性进展是随着GATA-3阴性肿瘤细胞群体的扩大而发生的。这些数据表明，GATA-3在乳腺癌中调节肿瘤分化并抑制肿瘤扩散。
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