title: Androgen receptors may act in a paracrine manner to regulate oesophageal adenocarcinoma growth.
abstract: BACKGROUND
  The role of androgen receptors (ARs) in tumorigenesis, including transcription of fibroblast growth factors (FGFs), is established in prostate cancer. This study examined the role of ARs and FGFs in oesophageal adenocarcinoma (EAC), where tumour incidence in males is higher.
  
  
  METHODS
  AR gene expression was analysed using quantitative RT-PCR; AR, fibroblast growth factor receptor-1 (FGFR-1) and fibroblast growth factor-8 isoform b (FGF-8b) protein by immunohistochemistry; and serum steroid levels (testosterone, progesterone, luteinising hormone and follicle stimulating hormone (FSH)) by immunoassay. A human oesophageal adenocarcinoma cell line was grown subcutaneously in nude mice.
  
  
  RESULTS
  AR gene expression was of significantly higher levels than oesophageal adenocarcinomas (n=21, p=0.002) and in the squamous carcinoma line (OE21) compared with the adenocarcinoma lines (OE33 and OE19). Median serum testosterone levels in oesophageal carcinoma patients were higher than in age-matched controls (p=0.01) and reduced postoperatively, in patients undergoing curative resection (p=0.006). No significant differences were observed in hormones except FSH, where preoperative levels were significantly higher in the EAC group. AR protein was expressed in normal oesophageal squamous epithelial cells and also in the stroma of 18/23 EAC samples. FGFR-1 protein was expressed in malignant epithelium of 23/23 tumour samples. OE19 xenografts grew faster in male versus female mice (tumour weight at day 21, 1.14 g and 0.28 g, respectively, p=0.005) and had elevated FGF receptor expression.
  
  
  CONCLUSIONS
  AR expressed in the stroma of oesophageal adenocarcinomas may induce paracrine effects following stimulation by androgens (including tumour-derived), possibly via FGFs, including FGF-8b.
authors.affiliation: Division of Pre-Clinical Oncology, University of Nottingham, D Floor, West Block, Queen's Medical Centre, University Hospital, Nottingham, NG7 2UH, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Awan
authors.forename: S Y
authors.initials: SY
authors.lastname: Iftikhar
authors.forename: T M
authors.initials: TM
authors.lastname: Morris
authors.forename: P A
authors.initials: PA
authors.lastname: Clarke
authors.forename: A M
authors.initials: AM
authors.lastname: Grabowska
authors.forename: N
authors.initials: N
authors.lastname: Waraich
authors.forename: S A
authors.initials: SA
authors.lastname: Watson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D015870:Gene Expression; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011944:Receptors, Androgen / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: C496456:FGF8 protein, human; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D017468:Receptors, Fibroblast Growth Factor; D051524:Fibroblast Growth Factor 8