title: D-glucuronyl C5-epimerase suppresses small-cell lung cancer cell proliferation in vitro and tumour growth in vivo.
abstract: BACKGROUND
  D-Glucuronyl C5-epimerase (GLCE) is a key enzyme involved in the biosynthesis of heparan sulphate proteoglycans, which has an important role in cell-cell and cell-matrix interactions and signalling. Decreased GLCE expression in human breast tumours and its anti-proliferative effects in breast cancer cells suggest that it may be a candidate tumour-suppressor gene. The aim of this study was to investigate the involvement of GLCE in lung carcinogenesis.
  
  
  METHODS
  D-Glucuronyl C5-epimerase expression in different lung cancer cell lines was determined and the gene was ectopically re-expressed in U2020 small-cell lung cancer cells. Cellular proliferation in vitro and tumour growth in vivo were then examined.
  
  
  RESULTS
  Ectopic re-expression of GLCE in U2020 cells did not affect cell viability but did influence morphology. Cellular proliferation in vitro and tumour formation in vivo were both suppressed. These effects were mediated via downregulation of several pro-angiogenic growth factors and their receptors, including VEGF-A, TGFB1, FGFR2, PDGF-A and PDGF-B, and TNFa and its receptors. Expression of matrix metalloproteinase2, MTA1, PLAU, TIMP3, S100A4, SERPINE1 and TWIST1 was also downregulated.
  
  
  CONCLUSIONS
  The anti-tumour effects associated with ectopic GLCE re-expression suggest that it may be a potential tumour-suppressor gene and a possible target for lung cancer diagnosis and treatment.
authors.affiliation: Institute of Molecular Biology and Biophysics SD RAMS, Timakova str 2, Novosibirsk 630117, Russia. elv_grig@yahoo.com
authors.forename: E V
authors.initials: EV
authors.lastname: Grigorieva
authors.forename: T Y
authors.initials: TY
authors.lastname: Prudnikova
authors.forename: N V
authors.initials: NV
authors.lastname: Domanitskaya
authors.forename: L A
authors.initials: LA
authors.lastname: Mostovich
authors.forename: T V
authors.initials: TV
authors.lastname: Pavlova
authors.forename: V I
authors.initials: VI
authors.lastname: Kashuba
authors.forename: E R
authors.initials: ER
authors.lastname: Zabarovsky
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002238:Carbohydrate Epimerases / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D002238:Carbohydrate Epimerases; C019591:heparosan N-sulfate D-glucuronosyl 5-epimerase