title: gamma-Glutamyl transpeptidase expression in Ewing's sarcoma cells: up-regulation by interferons.
abstract: The genetic hallmark of Ewing's sarcoma family of tumours (ET) is the presence of the translocation t(11;22)(q24;q12), which creates the ET fusion gene, leading to cellular transformation. Five human gamma-glutamyl transpeptidase (gamma-GT) genes are located near the chromosomal translocation in ET. gamma-GT is a major enzyme involved in glutathione homoeostasis. Five human cell lines representative of primary or metastatic tumours were investigated to study whether gamma-GT alterations could occur at the chromosomal breaks and rearrangements in ET. As shown by enzymic assays and FACS analyses, all ET cell lines consistently expressed a functional gamma-GT which however did not discriminate steps of ET progression. As shown previously [Sancéau, Hiscott, Delattre and Wietzerbin (2000) Oncogene 19, 3372-3383], ET cells respond to the antiproliferative effects of interferons (IFNs) type I (alpha and beta) and to a much less degree to IFN type II (gamma). IFN-alpha and -beta arrested cells in the S-phase of the cell cycle. We found an enhancement of gamma-GT mRNA species with IFN-alpha and -beta by reverse transcriptase-PCR analyses. This is reflected by up-regulation of gamma-GT protein, which coincides with the increase in gamma-GT-specific enzymic activity. Similarly, IFNs up-regulate the levels of gamma-GT in another IFN-responsive B cell line. Whether this up-regulation of gamma-GT by IFNs is of physiological relevance to cell behaviour remains to be studied.
authors.affiliation: Unité 365 INSERM, Section de Recherche, Institut Curie, 75248 Paris Cedex 05, France.
authors.forename: Lena
authors.initials: L
authors.lastname: Bouman
authors.forename: Josiane
authors.initials: J
authors.lastname: Sancéau
authors.forename: Dany
authors.initials: D
authors.lastname: Rouillard
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bauvois
mesh_terms: D001859:Bone Neoplasms / Q000201:enzymology* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D016158:Genes, p53; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016296:Mutagenesis; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000201:enzymology* / Q000235:genetics; D014407:Tumor Cells, Cultured; D005723:gamma-Glutamyltransferase / Q000235:genetics*
chemical_list: D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005723:gamma-Glutamyltransferase