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突变和功能分析表明,ST7是人类染色体7q31上一个高度保守的肿瘤抑制基因。

Mutational and functional analyses reveal that ST7 is a highly conserved tumor-suppressor gene on human chromosome 7q31.

作者信息

Zenklusen J C, Conti C J, Green E D

机构信息

Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Nat Genet. 2001 Apr;27(4):392-8. doi: 10.1038/86891.

Abstract

Loss of heterozygosity (LOH) of markers on human chromosome 7q31 is frequently encountered in a variety of human neoplasias, indicating the presence of a tumor-suppressor gene (TSG). By a combination of microcell-fusion and deletion-mapping studies, we previously established that this TSG resides within a critical region flanked by the genetic markers D7S522 and D7S677. Using a positional cloning strategy and aided by the availability of near-complete sequence of this genomic interval, we have identified a TSG within 7q31, named ST7 (for suppression of tumorigenicity 7; this same gene was recently reported in another context and called RAY1). ST7 is ubiquitously expressed in human tissues. Analysis of a series of cell lines derived from breast tumors and primary colon carcinomas revealed the presence of mutations in ST7. Introduction of the ST7 cDNA into the prostate-cancer-derived cell line PC3 had no effect on the in vitro proliferation of the cells, but abrogated their in vivo tumorigenicity. Our data indicate that ST7 is a TSG within chromosome 7q31 and may have an important role in the development of some types of human cancer.

摘要

在多种人类肿瘤中经常会出现人类染色体7q31上标记的杂合性缺失(LOH),这表明存在一个肿瘤抑制基因(TSG)。通过微细胞融合和缺失定位研究相结合,我们先前确定该TSG位于由遗传标记D7S522和D7S677侧翼的关键区域内。利用定位克隆策略并借助该基因组区间近乎完整的序列,我们在7q31内鉴定出一个TSG,命名为ST7(抑制致瘤性7;该相同基因最近在另一种情况下被报道并称为RAY1)。ST7在人类组织中普遍表达。对一系列源自乳腺肿瘤和原发性结肠癌的细胞系分析显示ST7中存在突变。将ST7 cDNA导入源自前列腺癌的细胞系PC3对细胞的体外增殖没有影响,但消除了它们的体内致瘤性。我们的数据表明ST7是7q31染色体上的一个TSG,可能在某些类型的人类癌症发生中起重要作用。

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