Gene expression profiling of breast cell lines identifies potential new basal markers

Gene expression profiling of breast cell lines identifies potential new basal markers
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DOI:
10.1038/sj.onc.1209254
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发表时间:
2006-04-01
期刊:
影响因子:
8
通讯作者:
Bertucci, F
Bertucci, F
中科院分区:
医学1区
文献类型:
--
作者:
Charafe-Jauffret, E;Ginestier, C;Bertucci, F

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更好地描述乳腺细胞系 (BCL) 的分子特征可能有助于发现适用于肿瘤样本的新标记物。我们进行了基因和蛋白质表达专业。分别使用全基因组 DNA 微阵列和“细胞微阵列”(CMA) 上的免疫组织化学 (IHC) 分析 31 BCL。全局层次聚类区分了两组 BCL:I 组对应于管腔细胞系,II 组对应于基底细胞系和间充质细胞系。根据已发表的“内在 500 个基因集”计算出的与质心的相关性将 15 个细胞系指定为管腔细胞系,8 个细胞系为基础细胞系,4 个细胞系为间充质细胞系。一组 1.233 个基因在基础样本和管腔样本之间存在差异表达。间充质亚型和基底亚型非常相似,仅通过 227 个基因进行区分。由管腔与基底鉴别基因编码的 10 种蛋白(CAV1、CD44、EGFR、MET、ETS1、GATA3、管腔细胞角蛋白 CK19、基底细胞角蛋白 CK5/6、CD10 和 ERM 蛋白 moesin)的表达证实了亚型分类和所识别标记的有效性。我们的 BCL 基底/管腔特征正确地对已发表的一系列肿瘤样本进行了正确的重新分类,这些样本最初用于识别分子亚型,这表明所识别的标记物应该对肿瘤分类有用,并且可能代表疾病管理的有希望的目标。
A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression pro. ling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published 'intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management.