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Titolo:
Acquisition of glutamine synthetase expression in human hepatocarcinogenesis - Relation to disease recurrence and possible regulation by ubiquitin-dependent proteolysis
Autore:
Osada, T; Sakamoto, M; Nagawa, H; Yamamoto, J; Matsuno, Y; Iwamatsu, A; Muto, T; Hirohashi, S;
Indirizzi:
Natl Canc Ctr, Res Inst, Div Pathol, Chuo Ku, Tokyo 104, Japan Natl Canc Ctr Tokyo Japan 104 nst, Div Pathol, Chuo Ku, Tokyo 104, Japan Univ Tokyo, Dept Surg, Div Surg Oncol, Bunkyo Ku, Tokyo, Japan Univ TokyoTokyo Japan pt Surg, Div Surg Oncol, Bunkyo Ku, Tokyo, Japan Natl Canc Ctr Hosp, Dept Surg, Chuo Ku, Tokyo, Japan Natl Canc Ctr Hosp Tokyo Japan r Hosp, Dept Surg, Chuo Ku, Tokyo, Japan Kirin Brewery Co Ltd, Cent Labs Key Technol, Kanagawa, Japan Kirin BreweryCo Ltd Kanagawa Japan t Labs Key Technol, Kanagawa, Japan
Titolo Testata:
CANCER
fascicolo: 4, volume: 85, anno: 1999,
pagine: 819 - 831
SICI:
0008-543X(19990215)85:4<819:AOGSEI>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
SHORT-LIVED PROTEIN; MAJOR ENERGY-SOURCE; HEPATOCELLULAR-CARCINOMA; ADENOMATOUS HYPERPLASIA; ORNITHINE AMINOTRANSFERASE; HETEROGENEOUS DISTRIBUTION; MAMMALIAN-CELLS; MESSENGER-RNA; METABOLISM; AMMONIA;
Keywords:
glutamine synthetase; ubiquitin; hepatocellular carcinoma; amino acid sequencing; two-dimensional gel electrophoresis; immunohistochemistry;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Hirohashi, S Natlananc Ctr, Res Inst, Div Pathol, Chuo Ku, 5-1-1 Tsukiji, Tokyo 104, Jap Natl Canc Ctr 5-1-1 Tsukiji Tokyo Japan 104 , Tokyo 104, Jap
Citazione:
T. Osada et al., "Acquisition of glutamine synthetase expression in human hepatocarcinogenesis - Relation to disease recurrence and possible regulation by ubiquitin-dependent proteolysis", CANCER, 85(4), 1999, pp. 819-831

Abstract

BACKGROUND. The authors previously reported increased ubiquitin (Ub) immuno-reactivity in hepatocellular carcinomas (HCCs) and suggested a possible correlation between changes in ubiquitinated protein levels and multistep hepatocarcinogenesis. The current study was performed to identify one of these ubiquitinated proteins (42 kDa) and to analyze the clinical significance of its accumulation. METHODS, The protein was purified using two-dimensional gel electrophoresis and identified by amino acid sequence analysis. The authors studied the expression of this protein in 101 HCCs and 23 precancerous lesions by immunohistochemical methods and in 26 HCCs by immunoblot analysis. A survival analysis was performed on patients with advanced HCC using the Kaplan-Meier method with approximate chi-square statistics for the log rank test. RESULTS. The target protein for ubiquitination was identified as glutaminesynthetase (GS). Accumulation of GS was found in 19 of 49 advanced HCCs (38.8%) by immunohistochemical methods and in 9 of 16 (56.3%) by immunoblot analysis, whereas the frequency was much lower in early HCCs (12.9% and 33.3%, respectively) and precancerous lesions (4.3% by immunostaining). In the Ub immunoblot analysis of strongly GS positive specimens, an intense 42-kDaubiquitinated band was observed. Nine of 21 (42.9%) nodule-in-nodule type HCCs showed a GS positive, high-grade component within a GS negative, low-grade component, indicating the acquisition of GS expression during progression. Among 23 patients with a single advanced HCC nodule, the relapse free survival time was significantly shorter in the GS positive group than in the GS negative group. CONCLUSIONS, The results of this study demonstrate the acquisition of GS expression during hepatocarcinogenesis and the possible regulation of GS enzyme activity by a Ub-dependent proteolytic system. Moreover, GS might play a significant role in promoting the metastatic potential of HCC. (C) 1999 American Cancer Society.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/21 alle ore 03:47:07