title: 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.
abstract: We performed next generation sequencing- and microarray-based gene expression profiling of CD44(+)/CD24(-)/CD45(-) breast CSCs (cancer stem cells) isolated from primary ERα-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 stemness, 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 ERα-positive breast cancer, the PI3K pathway which is involved in endocrine resistance is hyperactive.
authors: Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
authors: Olaf
authors: O
authors: Hardt
authors: Stefan
authors: S
authors: Wild
authors: Ilka
authors: I
authors: Oerlecke
authors: Kay
authors: K
authors: Hofmann
authors: Shujun
authors: S
authors: Luo
authors: Yvonne
authors: Y
authors: Wiencek
authors: Eva
authors: E
authors: Kantelhardt
authors: Christoph
authors: C
authors: Vess
authors: Geoffrey P
authors: GP
authors: Smith
authors: Gary P
authors: GP
authors: Schroth
authors: Andreas
authors: A
authors: Bosio
authors: Jürgen
authors: J
authors: Dittmer
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D051927:CD24 Antigen / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000032:analysis; D004967:Estrogens; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D007527:Isoenzymes / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012680:Sensitivity and Specificity; D059467:Transcriptome
chemical_list: D051927:CD24 Antigen; D047628:Estrogen Receptor alpha; D004967:Estrogens; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C497889:CD24 protein, human; C497483:CD44 protein, human; C506487:ESR1 protein, human