Highly sensitive profiling of CD44+/CD24- breast cancer stem cells by combining global mRNA amplification and next generation sequencing: Evidence for a hyperactive PI3K pathway

Highly sensitive profiling of CD44+/CD24- breast cancer stem cells by combining global mRNA amplification and next generation sequencing: Evidence for a hyperactive PI3K pathway
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DOI:
10.1016/j.canlet.2012.06.010
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发表时间:
2012-12-28
期刊:
影响因子:
9.7
通讯作者:
Dittmer, Juergen
Dittmer, Juergen
中科院分区:
医学1区
文献类型:
--
作者:
Hardt, Olaf;Wild, Stefan;Dittmer, Juergen

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我们对从原发性ER α阳性乳腺癌中分离的CD44(+)/CD24(-)/CD45(-)乳腺CSCs(癌症干细胞)进行了下一代测序和微阵列基因表达谱分析。通过结合半自动化解离人类肿瘤组织,磁性细胞分选和cDNA扩增需要少于500个CSCs进行转录组分析。除了参与严重度维持的基因过表达外,CSCs还显示出更高水平的PI3K通路驱动基因,包括EGFR、HB-EGF、PDGFRA/B、PDGF、MET、PIK3CA、PIK3R1和PIK3R2。这提示,在ER α阳性乳腺癌的CSCs中,参与内分泌抵抗的PI3K通路异常活跃。2012爱思唯尔爱尔兰有限公司版权所有。
We performed next generation sequencing- and microarray-based gene expression profiling of CD44(+)/CD24(-)/CD45(-) breast CSCs (cancer stem cells) isolated from primary ER alpha-positive breast cancer. By combining semi-automated dissociation of human tumor tissue, magnetic cell sorting and cDNA amplification less than 500 CSCs were required for transcriptome analyses. Besides overexpressing genes involved in maintenance of sternness, the CSCs showed higher levels of genes that drive the PI3K pathway, including EGFR, HB-EGF, PDGFRA/B, PDGF, MET, PIK3CA, PIK3R1 and PIK3R2. This suggests that, in CSCs of ER alpha-positive breast cancer, the PI3K pathway which is involved in endocrine resistance is hyperactive. (c) 2012 Elsevier Ireland Ltd. All rights reserved.