全基因组微阵列杂交的表达谱揭示了番茄红素暴露后乳腺癌细胞系基因表达的差异

Nasséra Chalabi , Samir Satih , Laetitia Delort , Yves-Jean Bignon , Dominique J. Bernard-Gallon
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引用次数: 39

摘要

饮食与基因表达变化之间的相关性是理解癌症途径的一个重要领域。我们使用泛基因组阵列检测了番茄红素对乳腺癌细胞系的影响。番茄红素主要来源于番茄和番茄制品有一些流行病学证据表明它对乳腺癌有预防作用。此前,我们使用专用乳腺癌微阵列研究了番茄红素在乳腺癌中的作用。为了证实这些结果并探索与乳腺癌相关的其他途径,在本研究中,我们使用了包含25,000个寡核苷酸的全基因组阵列。该体外研究检测了两种人乳腺癌细胞系(MCF-7和MDA-MB-231)和一种纤维囊性乳腺细胞系(MCF-10a),分别用10 μM番茄红素处理或不处理48小时。在cy3标记的番茄红素处理RNA和cy5标记的未处理RNA之间进行竞争杂交,以确定差异表达基因。通过t检验分析,发现391个基因子集在雌激素阳性细胞(MCF-7)和雌激素阴性细胞(MDA-MB-231, MCF-10a)之间受到番茄红素的差异调节。分层聚类发现乳腺癌细胞系MCF-7、MDA-MB-231与乳腺纤维囊性细胞系MCF-10a之间存在726个差异基因。在凋亡、细胞通讯、MAPK、细胞周期、外源代谢、脂肪酸生物合成、间隙连接细胞间通讯等多种分子通路中观察到基因表达的改变。
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Expression profiling by whole-genome microarray hybridization reveals differential gene expression in breast cancer cell lines after lycopene exposure

The correlation between diet and variation in gene-expression is an important field which could be considered to approach cancer pathways comprehension. We examined the effects of lycopene on breast cancer cell lines using pangenomic arrays. Lycopene is derived predominantly from tomatoes and tomato products and there is some epidemiologic evidence for a preventive role in breast cancer. Previously, we investigated lycopene in breast cancer using a dedicated breast cancer microarray. To confirm these results and explore pathways other than those implicated in breast cancer, for this study we used pangenomic arrays containing 25,000 oligonucleotides. This in vitro study assayed two human mammary cancer cell lines (MCF-7 and MDA-MB-231), and a fibrocystic breast cell line (MCF-10a) treated or not with 10 μM lycopene for 48 h. A competitive hybridization was performed between Cy3-labeled lycopene treated RNA and Cy5-labeled untreated RNA to define differentially expressed genes. Using t-test analysis, a subset of 391 genes was found to be differentially modulated by lycopene between estrogen-positive cells (MCF-7) and estrogen-negative cells (MDA-MB-231, MCF-10a). Hierarchical clustering revealed 726 discriminatory genes between breast cancer cell lines (MCF-7, MDA-MB-231) and the fibrocystic breast cell line (MCF-10a). Modified gene expression was observed in various molecular pathways, such as apoptosis, cell communication, MAPK and cell cycle as well as xenobiotic metabolism, fatty acid biosynthesis and gap junctional intercellular communication.

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