期刊
ONCOGENE
卷 22, 期 6, 页码 869-883出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1206216
关键词
C/EBP transcription factor; anchorage independence; EMT; invasion; mammary gland; retroviral vector
资金
- NCI NIH HHS [P30 CA68485, CA68485] Funding Source: Medline
- NIDDK NIH HHS [DK20593] Funding Source: Medline
The transcription factor CCAAT/enhancer binding protein (C/EBP)p is critical for normal growth and differentiation of the mammary gland. The intronless C/EBPbeta gene encodes a single mRNA that produces three protein isoforms, C/EBPbeta-1, -2, and -3, which share a common basic-leucine zipper domain at their C-terminus, but are distinguished at their N-termini by the in-frame methionine codon used to initiate translation. Although C/EBPbeta-1 and -2 are both transactivators, they likely perform distinct functions in mammary epithelial cells. C/EBPbeta-1 is the only isoform detected in normal human mammary tissue. In breast cancer cell lines, C/EBPbeta-1 is absent, and the C/EBPbeta-2 transactivator is expressed. Moreover, our data suggest that C/EBPbeta-2 is upregulated in human primary breast tumors. To assess C/EBPbeta-2's ability to participate in the transformation process, we generated recombinant retrovirus selectively encoding epitope-tagged C/EBPbeta-2. Strikingly, 10 days after infecting a normal human mammary epithelial cell line (MCF10A) with C/EBPbeta-2 virus, transformed subcultures were readily generated. Specifically, C/EBPbeta-2-overexpressing MCF10A cells form foci, gain anchorage independence, express markers associated with having undergone an epithelial-to-mesenchymal transition, and acquire an invasive phenotype. These studies, and our previous observations, provide supportive evidence that deregulated expression of C/EBPbeta-2 contributes to malignant conversion of the human breast.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据