GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model

被引：295

作者：

Kouros-Mehr, Hosein ^{[1
,2
]}

Bechis, Seth K. ^{[1
,2
]}

Slorach, Euan M. ^{[1
]}

Littlepage, Laurie E. ^{[1
]}

Egeblad, Mikala ^{[1
]}

Ewald, Andrew J. ^{[1
]}

Pai, Sung-Yun ^{[3
,4
]}

Ho, I-Cheng ^{[5
]}

Werb, Zena ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA

[3] Childrens Hosp, Combined Dept Pediat Hematol Oncol, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

来源：

CANCER CELL | 2008年 / 13卷 / 02期

关键词：

D O I：

10.1016/j.ccr.2008.01.011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：141 / 152

页数：12

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