Cross-platform expression profiling demonstrates that SV40 small tumor antigen activates Notch, Hedgehog, and Wnt signaling in human cells.

Cross-platform expression profiling demonstrates that SV40 small tumor antigen activates Notch, Hedgehog, and Wnt signaling in human cells.
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跨平台表达分析表明,SV40小肿瘤抗原激活了人类细胞中的缺口,刺猬和Wnt信号。

DOI:
10.1186/1471-2407-6-54
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发表时间:
2006-03-07
期刊:
影响因子:
3.8
通讯作者:
Moreno, CS
Moreno, CS
中科院分区:
医学2区
文献类型:
--
作者:
Ali-Seyed, M;Laycock, N;Karanam, S;Xiao, WM;Blair, ET;Moreno, CS

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我们先前使用Affymetrix U133 GeneChips分析了猴病毒40(SV40)小肿瘤抗原(ST)对人胚胎肾(HEK)细胞系基因表达的影响。为了交叉验证和扩展我们最初的发现,我们试图使用另一种微阵列平台来比较这些细胞系的表达谱。方法:我们利用应用生物系统(AB)微阵列平台,使用单个60聚体寡核苷酸和单色定量化学发光检测,分析了有和不表达SV40ST的匹配细胞系。结果:虽然我们以前使用Affymetrix平台仅能够识别456个受ST影响的基因,但是我们使用AB平台识别了1927个单独的基因。额外的技术重复将识别的基因数量增加到3478个基因,并确认了我们最初的456个基因中的278个(61%)的变化。在新发现的3200个受SV40 ST影响的基因中,我们通过QRT-PCR确认了20个基因,其中包括Wnt、Notch和Hedgehog信号通路的几个组成部分,这与SV40 ST激活这些发育通路是一致的。而Notch激活抑制剂对细胞存活无影响,而环多巴胺对表达SV40ST的细胞有较强的杀伤作用。结论:SV40ST的表达改变了细胞的生存途径,使细胞对Hedgehog途径抑制剂的杀伤作用敏感。
We previously analyzed human embryonic kidney (HEK) cell lines for the effects that simian virus 40 (SV40) small tumor antigen (ST) has on gene expression using Affymetrix U133 GeneChips. To cross-validate and extend our initial findings, we sought to compare the expression profiles of these cell lines using an alternative microarray platform. METHODS: We have analyzed matched cell lines with and without expression of SV40 ST using an Applied Biosystems (AB) microarray platform that uses single 60-mer oligonucleotides and single-color quantitative chemiluminescence for detection. RESULTS: While we were able to previously identify only 456 genes affected by ST with the Affymetrix platform, we identified 1927 individual genes with the AB platform. Additional technical replicates increased the number of identified genes to 3478 genes and confirmed the changes in 278 (61%) of our original set of 456 genes. Among the 3200 genes newly identified as affected by SV40 ST, we confirmed 20 by QRTPCR including several components of the Wnt, Notch, and Hedgehog signaling pathways, consistent with SV40 ST activation of these developmental pathways. While inhibitors of Notch activation had no effect on cell survival, cyclopamine had a potent killing effect on cells expressing SV40 ST. CONCLUSIONS: These data show that SV40 ST expression alters cell survival pathways to sensitize cells to the killing effect of Hedgehog pathway inhibitors.
DOI: 10.1101/gr.1048803
发表时间: 2003-07-01
期刊: GENOME RESEARCH
影响因子: 7
作者:
Barczak, A;Rodriguez, MW;Erle, DJ
通讯作者: Erle, DJ
DOI: 10.1186/1471-213x-2-8
发表时间: 2002-07-02
影响因子: --
作者:
Willert, Jennifer;Epping, Mirjam;Pollack, Jonathan R;Brown, Patrick O;Nusse, Roel
通讯作者: Nusse, Roel
DOI: 10.1073/pnas.091062498
发表时间: 2001-04-24
影响因子: 11.1
作者:
Tusher, VG;Tibshirani, R;Chu, G
通讯作者: Chu, G
DOI: 10.1093/nar/gkh353
发表时间: 2004-07-01
影响因子: 14.9
作者:
Karanam, S;Moreno, CS
通讯作者: Moreno, CS
DOI: 10.1126/science.281.5382.1509
发表时间: 1998-09-04
期刊: SCIENCE
影响因子: 56.9
作者:
He, TC;Sparks, AB;Kinzler, KW
通讯作者: Kinzler, KW