期刊
CANCER CELL
卷 13, 期 2, 页码 141-152出版社
CELL PRESS
DOI: 10.1016/j.ccr.2008.01.011
关键词
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资金
- NCI NIH HHS [U01 CA105379-03, CA057621, R01 CA057621-15, R01 CA057621-11, R01 CA057621-12, R01 CA057621-13, U01 CA105379, CA105379, U01 CA105379-04, R01 CA057621, U01 CA105379-05, U01 CA105379-02, R01 CA057621-14, U01 CA105379-01, R01 CA057621-10] Funding Source: Medline
- NIEHS NIH HHS [ES012801, U01 ES012801, U01 ES012801-05, U01 ES012801-010001] Funding Source: Medline
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.
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