Charafe-Jauffret E, Ginestier C, Monville F, Finetti P, Adélaïde J, Cervera N, Fekairi S, Xerri L, Jacquemier J, Birnbaum D, Bertucci F
Marseille Cancer Institute, Laboratory of Molecular Oncology, Inserm/Institut Paoli-Calmettes, Marseille, France.
Oncogene. 2006 Apr 6;25(15):2273-84. doi: 10.1038/sj.onc.1209254.
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 profiling 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.
对乳腺细胞系（BCL）进行更精细的分子特征分析，可能有助于发现可应用于肿瘤样本的新标志物。我们分别使用全基因组DNA微阵列和针对“细胞微阵列”（CMA）的免疫组织化学（IHC）技术，对31种BCL进行了基因和蛋白质表达谱分析。全局层次聚类区分出两组BCL：第一组对应于腔面细胞系，第二组对应于基底和间充质细胞系。与根据已发表的“内在500基因集”计算出的质心的相关性，将15种细胞系归类为腔面型，8种为基底型，4种为间充质型。在基底型和腔面型样本之间，有一组1233个基因存在差异表达。间充质型和基底型亚型相当相似，仅由227个基因区分。由腔面型与基底型鉴别基因编码的10种蛋白质（CAV1、CD44、EGFR、MET、ETS1、GATA3、腔面细胞角蛋白CK19、基底细胞角蛋白CK5/6、CD10和ERM蛋白埃兹蛋白）的表达，证实了亚型分类以及所鉴定标志物的有效性。我们的BCL基底/腔面特征正确地重新分类了最初用于鉴定分子亚型的已发表肿瘤样本系列，这表明所鉴定的标志物应有助于肿瘤分类，并且可能代表疾病管理中有前景的靶点。
