TUSC1, a putative tumor suppressor gene, reduces tumor cell growth in vitro and tumor growth in vivo.

TUSC1, a putative tumor suppressor gene, reduces tumor cell growth in vitro and tumor growth in vivo.
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TUSC1是一种推定的肿瘤抑制基因,可在体外减少肿瘤细胞的生长和体内肿瘤的生长。

DOI:
10.1371/journal.pone.0066114
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Wiest JS
Wiest JS
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shan Z;Shakoori A;Bodaghi S;Goldsmith P;Jin J;Wiest JS

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我们之前报道了从人肺癌染色体9p上D9S126纯合缺失区域分离到的新的无内含子基因TUSC1(肿瘤抑制候选基因1)的鉴定。在这项研究中,我们通过western blot检测了TUSC1在人肺癌细胞系中的差异表达,并通过免疫组织化学分析了TUSC1在原发性人肺癌组织微阵列中的差异表达。我们还通过体外和体内的生长抑制测试了TUSC1作为肿瘤抑制基因的功能活性和机制。结果显示,TUSC1纯合缺失的细胞中不表达TUSC1,在一些未缺失TUSC1的肿瘤细胞系中表达降低。有趣的是,来自原发性人肺癌组织微阵列的结果表明,TUSC1的高表达与肺癌患者的生存时间增加相关。我们的数据表明,转染TUSC1的肿瘤细胞系的生长曲线比转染空载体的肿瘤细胞系的生长曲线慢。更重要的是,在稳定转染TUSC1的细胞中,裸鼠体内的xenograph肿瘤生长明显慢于转染空载体的细胞。此外,共聚焦显微镜和免疫组织化学分析结果显示,TUSC1分布在肿瘤细胞系的细胞质和细胞核中,以及肺癌组织微阵列中的正常细胞和肿瘤细胞中。综上所述,我们的研究结果支持TUSC1作为位于染色体9p上的候选肿瘤抑制基因具有肿瘤抑制活性。
We previously reported the identification of TUSC1 (Tumor Suppressor Candidate 1), as a novel intronless gene isolated from a region of homozygous deletion at D9S126 on chromosome 9p in human lung cancer. In this study, we examine the differential expression of TUSC1 in human lung cancer cell lines by western blot and in a primary human lung cancer tissue microarray by immunohistochemical analysis. We also tested the functional activities and mechanisms of TUSC1 as a tumor suppressor gene through growth suppression in vitro and in vivo. The results showed no expression of TUSC1 in TUSC1 homozygously deleted cells and diminished expression in some tumor cell lines without TUSC1 deletion. Interestingly, the results from a primary human lung cancer tissue microarray suggested that higher expression of TUSC1 was correlated with increased survival times for lung cancer patients. Our data demonstrated that growth curves of tumor cell lines transfected with TUSC1 grew slower in vitro than those transfected with the empty vector. More importantly, xenograph tumors in nude mice grew significantly slower in vivo in cells stably transfected with TUSC1 than those transfected with empty vector. In addition, results from confocal microscopy and immunohistochemical analyses show distribution of TUSC1 in the cytoplasm and nucleus in tumor cell lines and in normal and tumor cells in the lung cancer tissue microarray. Taken together, our results support TUSC1 has tumor suppressor activity as a candidate tumor suppressor gene located on chromosome 9p.
DOI: 10.1038/sj.onc.1207857
发表时间: 2004-08-26
期刊: ONCOGENE
影响因子: 8
作者:
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DOI: 10.1158/1078-0432.ccr-03-0489
发表时间: 2004-07-01
影响因子: 11.5
作者:
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