title: Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations.
abstract: BACKGROUND
  Estrogen receptor positive breast cancers have high recurrence rates despite tamoxifen therapy. Breast cancer stem/progenitor cells (BCSCs) initiate tumors, but expression of estrogen (ER) or progesterone receptors (PR) and response to tamoxifen is unknown. Interleukin-6 (IL-6) and interleukin-8 (IL-8) may influence tumor response to therapy but expression in BCSCs is also unknown.
  
  
  METHODS
  BCSCs were isolated from breast cancer and benign surgical specimens based on CD49f/CD24 markers. CD44 was measured. Gene and protein expression of ER alpha, ER beta, PR, IL-6 and IL-8 were measured by proximity ligation assay and qRT-PCR.
  
  
  RESULTS
  Gene expression was highly variable between patients. On average, BCSCs expressed 10-106 fold less ERα mRNA and 10-103 fold more ERβ than tumors or benign stem/progenitor cells (SC). BCSC lin-CD49f-CD24-cells were the exception and expressed higher ERα mRNA. PR mRNA in BCSCs averaged 10-104 fold less than in tumors or benign tissue, but was similar to benign SCs. ERα and PR protein detection in BCSCs was lower than ER positive and similar to ER negative tumors. IL-8 mRNA was 10-104 higher than tumor and 102 fold higher than benign tissue. IL-6 mRNA levels were equivalent to benign and only higher than tumor in lin-CD49f-CD24-cells. IL-6 and IL-8 proteins showed overlapping levels of expressions among various tissues and cell populations.
  
  
  CONCLUSIONS
  BCSCs and SCs demonstrate patient-specific variability of gene/protein expression. BCSC gene/protein expression may vary from that of other tumor cells, suggesting a mechanism by which hormone refractory disease may occur.
authors.forename: Robynn V
authors.initials: RV
authors.lastname: Schillace
authors.forename: Amy M
authors.initials: AM
authors.lastname: Skinner
authors.forename: Rodney F
authors.initials: RF
authors.lastname: Pommier
authors.forename: Steven
authors.initials: S
authors.lastname: O'Neill
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Muller
authors.forename: Arpana M
authors.initials: AM
authors.lastname: Naik
authors.forename: Juliana E
authors.initials: JE
authors.lastname: Hansen
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, Mail Code L619, 3181 SW Sam Jackson Park Rd, Portland, OR 97239-3011, USA. pommiers@ohsu.edu.
authors.forename: SuEllen J
authors.initials: SJ
authors.lastname: Pommier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018960:Hyaluronan Receptors; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D011980:Receptors, Progesterone