An RNA-seq-based gene expression profiling of radiation-induced tumorigenic mammary epithelial cells.
An RNA-seq-based gene expression profiling of radiation-induced tumorigenic mammary epithelial cells.
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基于 RNA-seq 的辐射诱导致瘤乳腺上皮细胞基因表达谱分析
DOI：
10.1016/j.gpb.2012.11.001
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发表时间：
2012-12
影响因子：
9.5
通讯作者：
Yu, Jun
中科院分区：
文献类型：
--
作者：
Ma, Lina;Nie, Linghu;Liu, Jing;Zhang, Bing;Song, Shuhui;Sun, Min;Yang, Jin;Yang, Yadong;Fang, Xiangdong;Hu, Songnian;Zhao, Yongliang;Yu, Jun
永生性和致瘤性是癌症的两个明显特征。永生化被认为先于肿瘤发生。为了了解乳腺上皮致瘤性和癌症进展的分子机制，我们通过重离子辐射永生细胞模型建立了致瘤细胞模型，该模型是通过在正常人乳腺上皮细胞中过表达人端粒酶逆转录酶（hTERT）而建立的。我们使用hTERT过表达永生细胞系（I_hMEC）作为对照，检查了该致瘤细胞系（T_hMEC）的表达谱。通过使用下一代测序（NGS）平台（Life Technologies SOLiD 3）生成深入的RNA-seq数据。我们发现，管家（HK）和组织特异性（TS）基因的差异调节在肿瘤发生过程中。HK基因倾向于被激活，而TS基因倾向于被抑制。此外，HK基因和TS基因倾向于在不同的RPKM（每百万个映射序列读段中每个外显子内切酶读段的基因表达）水平上差异地贡献基因表达的变化。基于两种细胞系的转录组分析，我们定义了7053个永生和致瘤性之间的差异表达基因（DEG）。使用qRT-PCR进一步验证20个手动选择的基因的差异表达。我们的观察可能有助于我们进一步了解从永生化到肿瘤发生的细胞机制。
Immortality and tumorigenicity are two distinct characteristics of cancers. Immortalization has been suggested to precede tumorigenesis. To understand the molecular mechanisms of tumorigenicity and cancer progression in mammary epithelium, we established a tumorigenic cell model by means of heavy-ion radiation of an immortal cell model, which was created by overexpressing the human telomerase reverse transcriptase (hTERT) in normal human mammary epithelial cells. We examined the expression profile of this tumorigenic cell line (T_hMEC) using the hTERT-overexpressing immortal cell line (I_hMEC) as a control. In-depth RNA-seq data was generated by using the next-generation sequencing (NGS) platform (Life Technologies SOLiD3). We found that house-keeping (HK) and tissue-specific (TS) genes were differentially regulated during the tumorigenic process. HK genes tended to be activated while TS genes tended to be repressed. In addition, the HK genes and TS genes tended to contribute differentially to the variation of gene expression at different RPKM (gene expression in reads per exon kilobase per million mapped sequence reads) levels. Based on transcriptome analysis of the two cell lines, we defined 7053 differentially-expressed genes (DEGs) between immortality and tumorigenicity. Differential expression of 20 manually-selected genes was further validated using qRT-PCR. Our observations may help to further our understanding of cellular mechanism(s) in the transition from immortalization to tumorigenesis.
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影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
4.6
作者：
Shao, Genze;Balajee, Adayabalam S.;Zhao, Yongliang
通讯作者：
Zhao, Yongliang
影响因子：
3.8
作者：
Kirkpatrick, KL;Ogunkolade, W;Mokbel, K
通讯作者：
Mokbel, K
DOI：
10.1073/pnas.0932692100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Sorlie, T;Tibshirani, R;Botstein, D
通讯作者：
Botstein, D