γ-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.

<p>A Novel Prognostic Scoring Model Based on Albumin and γ-Glutamyltransferase for Hepatocellular Carcinoma Prognosis</p>

“…27 Moreover, there is increasing evidence indicating that systemic inflammatory response plays an important role in cancer progression. 28 Our data showed that ALB and GGT are predictors for patients with HCC after curative hepatectomy over a long-term followup, and revealed that preoperative decreased ALB levels and elevated GGT levels were significantly associated with shorter OS and RFS.…”

High pretreatment serum gamma-glutamyl transpeptidase predicts an inferior outcome in nasopharyngeal carcinoma

“…The pro-oxidant reactions produced by GGT could supplement endogenous Reactive oxygen species (ROS) in cancer cells, and endogenous ROS can contribute to the ‘persistent oxidative stress’, which is described as a factor in genomic instability and carcinogenesis [ 42 ]. Furthermore, a great number of cytokines including tumor necrosis factor alpha (TNF-alpha) [ 43 ], and interferon (IFN)-alpha and -beta [ 44 ], could induce GGT mRNA expression. These results indicate a connection between inflammation and GGT expression, not just as a response to inflammation-related oxidative stress, but rather as the effect of specific inflammatory cytokines.…”

Artificial Neural Network Model to Predict Post-Hepatectomy Early Recurrence of Hepatocellular Carcinoma without Macroscopic Vascular Invasion

“…High GGT levels may lead to liver dysfunction via inducing DNA instability, tumorigenesis and cancer progression. In addition, high GGT levels can predict the poor prognosis of HCC [49,50] High AFP levels indicate that the tumor is highly aggressive as well as the probability of intra-hepatic metastasis being usually greater than in patients with low AFP levels [51]. Other studies have repeatedly reported that a larger tumour diameter is signi cantly associated with PHER [52] and that MVI, satellite nodules and tumor differentiation are related to worse PHER [53][54][55].…”