RecQL4 helicase amplification is involved in human breast tumorigenesis.
RecQL4 helicase amplification is involved in human breast tumorigenesis.
复制标题
RecQL4 解旋酶扩增参与人类乳腺肿瘤发生
DOI：
10.1371/journal.pone.0069600
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Fang H;Nie L;Chi Z;Liu J;Guo D;Lu X;Hei TK;Balajee AS;Zhao Y
乳腺癌有遗传性和散发性两种形式，后者占妇女乳腺癌病例的绝大多数。在乳腺癌细胞和组织中经常观察到涉及8号染色体的数量和结构改变，短臂（8 p）缺失和长臂（8 q）增加。在这项研究中，我们发现，大多数人乳腺肿瘤细胞系检查显示8 q24的过度代表性，染色体位点RecQL 4区域映射，因此，RecQL 4表达水平显着升高。在检查的大多数临床乳腺肿瘤样品（38/43）中也观察到RecQL 4 mRNA水平增加。在MDA-MB 453乳腺癌细胞中，shRNA介导的RecQL 4抑制不仅显著抑制体外克隆形成存活和体内致瘤性。进一步的研究表明，RecQL 4与主要的生存因子Survivin相互作用，其蛋白水平影响Survivin的表达。虽然由于基因突变导致的RecQL 4功能丧失与具有早衰和癌症易感性特征的人类RTS的发生有因果关系，但我们的研究提供了证据，表明由于基因扩增导致的RecQL 4过表达在人类乳腺肿瘤进展中起关键作用。
Breast cancer occur both in hereditary and sporadic forms, and the later one comprises an overwhelming majority of breast cancer cases among women. Numerical and structural alterations involving chromosome 8, with loss of short arm (8p) and gain of long arm (8q), are frequently observed in breast cancer cells and tissues. In this study, we show that most of the human breast tumor cell lines examined display an over representation of 8q24, a chromosomal locus RecQL4 is regionally mapped to, and consequently, a markedly elevated level of RecQL4 expression. An increased RecQL4 mRNA level was also observed in a majority of clinical breast tumor samples (38/43) examined. shRNA-mediated RecQL4 suppression in MDA-MB453 breast cancer cells not only significantly inhibit the in vitro clonogenic survival and in vivo tumorigenicity. Further studies demonstrate that RecQL4 physically interacts with a major survival factor-survivin and its protein level affects survivin expression. Although loss of RecQL4 function due to gene mutations causally linked to occurrence of human RTS with features of premature aging and cancer predisposition, our studies provide the evidence that overexpression of RecQL4 due to gene amplification play a critical role in human breast tumor progression.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-11-1944
发表时间：
2011-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Bhattacharya A;Roy R;Snijders AM;Hamilton G;Paquette J;Tokuyasu T;Bengtsson H;Jordan RC;Olshen AB;Pinkel D;Schmidt BL;Albertson DG
通讯作者：
Albertson DG
影响因子：
4.8
作者：
Ghazani, Arezou A.;Arneson, Nona;Done, Susan J.
通讯作者：
Done, Susan J.
影响因子：
82.9
作者：
Ambrosini, G;Adida, C;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
4.8
作者：
Fan, Wei;Luo, Jianyuan
通讯作者：
Luo, Jianyuan
影响因子：
64.8
作者：
Evan, GI;Vousden, KH
通讯作者：
Vousden, KH