title: Analysis of hypoxia-associated gene expression in prostate cancer: lysyl oxidase and glucose transporter-1 expression correlate with Gleason score.
abstract: Prostate cancer cells exist under hypoxic conditions. Hypoxia has a detrimental effect on the efficacy of treatment and final outcome in patients with prostate cancer. There have been a large number of endogenous markers of hypoxia described previously across a range of cancer types, both in vitro and in vivo. The aim of this study was to evaluate the expression of a range of hypoxia-associated genes within benign prostatic hypertrophy (BPH) and prostate cancer tissue. Messenger RNA was extracted from primary prostate tissue obtained from 67 men with benign prostatic hypertrophy or prostate cancer (Gleason score 5 to 10). Real-time polymerase chain reaction was performed to quantify the expression levels of 12 hypoxia-associated genes in these tissues. Expression of lysyl oxidase (LOX) and glucose transporter-1 (GLUT-1) genes were significantly higher in prostate cancer compared with BPH tissue (P<0.05) and correlated with Gleason score (LOX: R=0.297, P=0.015; GLUT-1: R=0.274, P=0.026). HIF-2alpha had a negative correlation with Gleason score (R= -0.309, P=0.012). The remaining hypoxia-associated genes did not show any specific pattern of expression in prostate tissue. Numerous molecules have been proposed as endogenous markers of hypoxia. The findings of this study illustrate that not all hypoxia-associated molecules are relevant to prostate cancer in vivo. However, LOX and GLUT-1 are candidate markers of hypoxia in prostate cancer and may prove useful in identifying patients with hypoxic prostate cancer. Not all hypoxia-associated molecules are relevant in prostate cancer in vivo.
authors.affiliation: Prostate Research Group, Edinburgh Cancer Research Centre, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. grant.stewart@ed.ac.uk
authors.forename: Grant D
authors.initials: GD
authors.lastname: Stewart
authors.forename: Kelly
authors.initials: K
authors.lastname: Gray
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Pennington
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Edwards
authors.forename: Antony C P
authors.initials: AC
authors.lastname: Riddick
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.forename: Fouad K
authors.initials: FK
authors.lastname: Habib
mesh_terms: D017931:DNA Primers / Q000737:chemistry; D019281:Dimerization; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D008297:Male; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D051272:Glucose Transporter Type 1; D012334:RNA, Neoplasm; C495677:SLC2A1 protein, human; D008249:Protein-Lysine 6-Oxidase; D010100:Oxygen