Structure and transcriptional regulation of the human mammaglobin gene, a breast cancer associated member of the uteroglobin gene family localized to chromosome 11q13

被引:83
作者
Watson, MA
Darrow, C
Zimonjic, DB
Popescu, NC
Fleming, TP
机构
[1] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63110 USA
[3] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA
关键词
mammaglobin; breast cancer; genomic organization; promoter;
D O I
10.1038/sj.onc.1201597
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mammaglobin gene encodes a novel secreted protein whose corresponding mRNA is frequently up-regulated in human breast cancer, In non-malignant tissues, expression is also strictly limited to the mammary epithelium. To better understand the mechanisms controlling these patterns of expression, we have isolated the human mammaglobin gene and performed an initial assessment of its promoter activity, Mammaglobin gene architecture is very similar to that of a family of related genes that includes uteroglobin and rat prostatein subunits C1, C2, and C3. However, the mammaglobin gene itself is not well conserved phylogenetically. The human mammaglobin gene is localized by fluorescent in situ hybridization to chromosome 11 band q13, a genomic region frequently amplified in breast neoplasia, The sequence of proximal 1 kb of mammaglobin promoter contains several potential transcriptional control elements and directs high-level expression of a transfected reporter construct in human breast tumor cell lines, However, comparable levels of reporter gene expression are also seen in non-mammary human cell lines, These data suggest that, unlike related gene family members, the striking breast-specific expression and tumor-associated overexpression of mammaglobin is mediated by complex transcriptional control at more distal sequence elements,.
引用
收藏
页码:817 / 824
页数:8
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