LY6K is a novel molecular target in bladder cancer on basis of integrate genome-wide profiling.
LY6K is a novel molecular target in bladder cancer on basis of integrate genome-wide profiling.
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DOI：
10.1038/sj.bjc.6605990
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发表时间：
2011-01-18
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究旨在通过对膀胱癌（BC）进行染色体改变分析和基于芯片的基因表达分析，寻找新的分子靶点。我们研究了一种癌睾抗原LY6K，其定位于8q24.3染色体。
对5种膀胱癌细胞系采用含244000个探针的高分辨率芯片比较基因组杂交技术进行分析。通过实时逆转录聚合酶链反应（RT - PCR）评估膀胱癌细胞系和临床膀胱癌标本中LY6K信使核糖核酸（mRNA）的表达水平。对细胞系进行LY6K荧光原位杂交检测。通过细胞生长实验、伤口愈合实验和基质胶侵袭实验评估细胞活力。
在所有细胞系中均观察到典型的获得性基因座（P < 0.0001），分别位于6p21.33 - p21.32、8q24.3、9q34.13、11q13.1 - q14.1、12q13.12 - q13.13、16p13.3和20q11.21 - q13.33。我们聚焦于LY6K基因所在的8q24.3基因座，它在膀胱癌细胞系的基因谱中上调最为显著。91例膀胱癌组织中LY6K mRNA的表达水平显著高于37例正常膀胱上皮组织（P < 0.0001）。荧光原位杂交证实，LY6K mRNA的高表达是由于该基因所在区域的基因扩增所致。细胞活力实验表明，LY6K基因敲低的膀胱癌细胞系在细胞生长、迁移和侵袭方面受到显著抑制；在稳定转染LY6K的细胞系中观察到相反的现象；而对转染细胞系进行LY6K基因敲低后，其恢复到转染前的原始表型。
位于8q24.3获得性基因座上的致癌基因LY6K的上调可能促进膀胱癌的发生发展。
The aim of this study is to find a novel molecular target based on chromosomal alteration and array-based gene expression analyses in bladder cancer (BC). We investigated a cancer testis antigen, LY6K, which is located on chromosome 8q24.3. Five BC cell lines were subjected to high-resolution array-comparative genomic hybridisation with 244 000 probes. The expression levels of LY6K mRNA were evaluated in BC cell lines and clinical BC specimens by real-time reverse transcription–PCR. The cell lines were subjected to fluorescence in situ hybridisation of LY6K. Cell viability was evaluated by cell growth, wound healing, and matrigel invasion assays. Typical gained loci (P<0.0001) at 6p21.33-p21.32, 8q24.3, 9q34.13, 11q13.1-q14.1, 12q13.12-q13.13, 16p13.3, and 20q11.21-q13.33 were observed in all of the cell lines. We focused on 8q24.3 locus where LY6K gene harbours, and it was the top upregulated one in the gene profile from the BC cell line. LY6K mRNA expression was significantly higher in 91 BCs than in 37 normal bladder epitheliums (P<0.0001). Fluorescence in situ hybridisation validated that the high LY6K mRNA expression was due to gene amplification in the region where the gene harbours. Cell viability assays demonstrated that significant inhibitions of cell growth, migration, and invasion occured in LY6K knock down BC cell lines; converse phenomena were observed in a stable LY6K transfectant; and LY6K knockdown of the transfectant retrieved the original phenotype from the LY6K transfectant. Upregulation of the oncogenic LY6K gene located on the gained locus at 8q24.3 may contribute BC development.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
11.5
作者：
Blaveri, E;Brewer, JL;Waldman, FM
通讯作者：
Waldman, FM
影响因子：
6.4
作者：
Qiu, Dongmei;Katanoda, Kota;Sobue, Tomotaka
通讯作者：
Sobue, Tomotaka
DOI：
10.1073/pnas.162471999
发表时间：
2002-10-01
影响因子：
11.1
作者：
Pollack, JR;Sorlie, T;Brown, PO
通讯作者：
Brown, PO
影响因子：
5.2
作者：
Choi, Suh Hee;Kong, Hyun Kyung;Park, Jong Hoon
通讯作者：
Park, Jong Hoon