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Titolo:
Expression of heavy subunit of gamma-glutamylcysteine synthetase (gamma-GCSh) in human colorectal carcinoma
Autore:
Tatebe, S; Unate, H; Sinicrope, FA; Sakatani, T; Sugamura, K; Makino, M; Ito, H; Savaraj, N; Kaibara, N; Kuo, MT;
Indirizzi:
Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 r, Dept Mol Pathol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med & Nutr, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 estinal Med & Nutr, Houston, TX 77030 USA Tottori Univ, Dept Pathol 1, Tottori 680, Japan Tottori Univ Tottori Japan 680 i Univ, Dept Pathol 1, Tottori 680, Japan Tottori Univ, Fac Med, Dept Surg 1, Tottori 680, Japan Tottori Univ Tottori Japan 680 Fac Med, Dept Surg 1, Tottori 680, Japan VA Med Ctr, Miami, FL USA VA Med Ctr Miami FL USAVA Med Ctr, Miami, FL USA
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 1, volume: 97, anno: 2002,
pagine: 21 - 27
SICI:
0020-7136(20020101)97:1<21:EOHSOG>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
MRP/GS-X PUMP; FAMILIAL ADENOMATOUS POLYPOSIS; ANTIOXIDANT RESPONSE ELEMENT; HUMAN GLIOMA-CELLS; NITRIC-OXIDE; COLON-CANCER; OXIDATIVE STRESS; GENE-EXPRESSION; LIGHT SUBUNIT; INDUCTION;
Keywords:
gamma-GCSh; MRP1; colorectal neoplasin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Kuo, MT Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Box 89,1515 Holcombe Blvd, Houston, TX 77030 USA Univ Texas Box 89,1515 Holcombe Blvd Houston TX USA 77030 7030 USA
Citazione:
S. Tatebe et al., "Expression of heavy subunit of gamma-glutamylcysteine synthetase (gamma-GCSh) in human colorectal carcinoma", INT J CANC, 97(1), 2002, pp. 21-27

Abstract

Gamma-glutamylcysteine synthetase (gamma -GCS) is a heterodimer consistingof heavy (gamma -GCSh) and light (gamma -GCSI) subunits. gamma -GCS catalyzes the rate-limiting de novo biosynthesis of glutathione (GSH), an abundant physiological antioxidant that plays important roles for regulating oxidative stress. Expression of gamma -GCSh and gamma -GCSI are sensitive to oxidative stress. To investigate whether expression of gamma -GCS is correlated with tumor progression, we used immunohistochemical approaches to examine16 human colorectal adenomas and resected 57 carcinomas from untreated patients. In adjacent normal colorectal epithelium, levels of gamma -GCSh expression were low. Strong cytoplasmic staining for gamma -GCSh was detected in 3 (18.8%) adenoma and 48 (84.2%) carcinomas. The frequency of gamma -GCShexpression in carcinoma was significantly higher than in adenoma (p < 0.0001). We used RNase protation assay and Western blot to determine levels of gamma -GCSh mRNA and protein from 10 pairs of matched carcinomas with adjacent normal controls. Elevated expression of both gamma -GCSh mRNA and protein were found in 6 cases, suggesting that transcriptional and for posttranscriptional regulation play an important role in the upregulation of gamma -GCS during colorectal carcinogenesis. We also examined the expression of another redox-regulated gene, multidrug resistance protein I (MRPI). Strong staining for MRPI was detected in I (6.3%) adenoma and 40 (70.2%) carcinomas. The frequency of MRPI expression in carcinoma was significantly higher than in adenoma ( p < 0.0001). Nuclear p53 expression was detected in 30 (52.6%) of carcinomas. There is a significant correlation between gamma -GCSh and MRP I expression (p = 0.013) but not between gamma -GCSh and p53. Since gamma -GCS is a sensor of oxidative stress, these results are consistent with the notion that oxidative stress is associated with colorectal tumor progression. (C) 2002 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 01:51:46