Gene expression profiling of tumours derived from rasV12/EIA-transformed mouse embryonic fibroblasts to identify genes required for tumour development

Gene expression profiling of tumours derived from rasV12/EIA-transformed mouse embryonic fibroblasts to identify genes required for tumour development
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DOI:
10.1186/1476-4598-4-4
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发表时间:
2005-01-16
期刊:
影响因子:
37.3
通讯作者:
Iovanna, Juan L.
Iovanna, Juan L.
中科院分区:
医学1区
文献类型:
--
作者:
Vasseur, Sophie;Malicet, Cedric;Iovanna, Juan L.

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背景:在癌症中,细胞转化之后伴随着肿瘤的发展。对转化机制的认识,包括原癌基因的激活和肿瘤抑制基因的失活,已经有了相当大的进步,而对肿瘤的发展仍然知之甚少。获得关于肿瘤进展机制的信息的一个有趣的方法是识别在肿瘤形成过程中其表达发生变化的基因。我们使用基于Affymetrix的DNA微阵列技术分析了ras(V12)/EIA转化的小鼠胚胎成纤维细胞来源的肿瘤的基因表达谱,以确定可能与肿瘤发生有关的基因。结果:在本研究分析的12,000个基因中,只有489个基因在肿瘤发生过程中发生了表达变化,213个基因上调,276个基因下调。这些差异表达的基因涉及多种细胞功能,包括转录调控、mRNA成熟和加工调控、蛋白质翻译调控、干扰素诱导基因激活、细胞内信号传导、细胞凋亡、细胞生长、血管生成、细胞骨架、细胞间相互作用、细胞外基质形成、代谢和分泌因子的产生。结论:本工作中发现的一些基因在ras(V12)/EIA转化后表达发生改变,可能成为新的肿瘤治疗靶点。
Background: In cancer, cellular transformation is followed by tumour development. Knowledge on the mechanisms of transformation, involving activation of proto-oncogenes and inactivation of tumour-suppressor genes has considerably improved whereas tumour development remains poorly understood. An interesting way of gaining information on tumour progression mechanisms would be to identify genes whose expression is altered during tumour formation. We used the Affymetrix-based DNA microarray technology to analyze gene expression profiles of tumours derived from ras(V12)/EIA-transformed mouse embryo fibroblasts in order to identify the genes that could be involved in tumour development.Results: Among the 12,000 genes analyzed in this study, only 489 showed altered expression during tumour development, 213 being up-regulated and 276 down-regulated. The genes differentially expressed are involved in a variety of cellular functions, including control of transcription, regulation of mRNA maturation and processing, regulation of protein translation, activation of interferon-induced genes, intracellular signalling, apoptosis, cell growth, angiogenesis, cytoskeleton, cell-to-cell interaction, extracellular matrix formation, metabolism and production of secretory factors.Conclusions: Some of the genes identified in this work, whose expression is altered upon ras(V12)/EIA transformation of MEFs, could be new cancer therapeutic targets.