title: Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism.
abstract: BACKGROUND
  Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response.
  
  
  METHODS
  Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test.
  
  
  RESULTS
  While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression.
  
  
  CONCLUSIONS
  The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. gordonni@ohsu.edu.
authors: Nicole
authors: N
authors: Gordon
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. skinner@ohsu.edu.
authors: Amy M
authors: AM
authors: Skinner
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. pommierr@ohsu.edu.
authors: Rodney F
authors: RF
authors: Pommier
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. schillacer@gmail.com.
authors: Robynn V
authors: RV
authors: Schillace
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. oneill.stevenc@gmail.com.
authors: Steven
authors: S
authors: O'Neill
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. alabran@ohsu.edu.
authors: Jennifer L
authors: JL
authors: Peckham
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. mullerp@ohsu.edu.
authors: Patrick
authors: P
authors: Muller
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. condron@ohsu.edu.
authors: Mary E
authors: ME
authors: Condron
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. donovan@ohsu.edu.
authors: Cory
authors: C
authors: Donovan
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. naika@ohsu.edu.
authors: Arpana
authors: A
authors: Naik
authors: Department of Surgery, Division of Plastic & Reconstructive Surgery, Oregon Health & Science University, Portland, OR, USA. hansenju@ohsu.edu.
authors: Juliana
authors: J
authors: Hansen
authors: Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code L619, Portland, OR, 97239, USA. pommiers@ohsu.edu.
authors: SuEllen J
authors: SJ
authors: Pommier
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D006019:Glycolysis; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt