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基于全基因组分析,LY6K 是膀胱癌的一个新的分子靶标。

LY6K is a novel molecular target in bladder cancer on basis of integrate genome-wide profiling.

机构信息

Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

出版信息

Br J Cancer. 2011 Jan 18;104(2):376-86. doi: 10.1038/sj.bjc.6605990. Epub 2010 Nov 9.

DOI:10.1038/sj.bjc.6605990
PMID:21063397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3031884/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Upregulation of the oncogenic LY6K gene located on the gained locus at 8q24.3 may contribute BC development.

摘要

背景

本研究旨在通过染色体改变和基于阵列的基因表达分析在膀胱癌(BC)中找到一个新的分子靶标。我们研究了位于 8q24.3 上的癌症睾丸抗原 LY6K。

方法

对 5 个 BC 细胞系进行了 244000 个探针的高分辨率阵列比较基因组杂交。通过实时逆转录-PCR 评估了 LY6K mRNA 在 BC 细胞系和临床 BC 标本中的表达水平。对 LY6K 的细胞系进行了荧光原位杂交。通过细胞生长、伤口愈合和基质胶侵袭测定评估细胞活力。

结果

在所有细胞系中均观察到典型的获得性位点(P<0.0001),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。我们专注于 8q24.3 基因座,该基因座是 BC 细胞系基因谱中上调最显著的基因座。91 例 BC 中 LY6K mRNA 表达明显高于 37 例正常膀胱上皮(P<0.0001)。荧光原位杂交验证了高 LY6K mRNA 表达是由于该基因所在区域的基因扩增。细胞活力测定表明,在 LY6K 敲低的 BC 细胞系中,细胞生长、迁移和侵袭明显受到抑制;在稳定转染的 LY6K 中观察到相反的现象;LY6K 敲低的转染体从 LY6K 转染体中恢复了原始表型。

结论

位于 8q24.3 获得性基因座上的致癌 LY6K 基因的上调可能有助于 BC 的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/bb20396d2b4a/6605990f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/98c2aba379fa/6605990f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/bfd7a2f6249f/6605990f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/9f8f2430c629/6605990f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/9c8eed9f3528/6605990f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/f78ff3afbc5e/6605990f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/bb20396d2b4a/6605990f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/98c2aba379fa/6605990f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/bfd7a2f6249f/6605990f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/9f8f2430c629/6605990f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/9c8eed9f3528/6605990f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/f78ff3afbc5e/6605990f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3ff/3031884/bb20396d2b4a/6605990f6.jpg

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