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Titolo:
Regulation of glut1 mRNA by hypoxia-inducible factor-1 - Interaction between H-ras and hypoxia
Autore:
Chen, CH; Pore, N; Behrooz, A; Ismail-Beigi, F; Maity, A;
Indirizzi:
Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 iat Oncol, Philadelphia, PA 19104 USA Case Western Reserve Univ, Sch Med, Dept Med & Mol Biol & Microbiol, Cleveland, OH 44106 USA Case Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 12, volume: 276, anno: 2001,
pagine: 9519 - 9525
SICI:
0021-9258(20010323)276:12<9519:ROGMBH>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUCOSE-TRANSPORTER GENE; ENDOTHELIAL GROWTH-FACTOR; FACTOR 1-ALPHA; TUMOR ANGIOGENESIS; HUMAN CANCER; EXPRESSION; ONCOGENES; CELLS; TRANSCRIPTION; PATHWAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Maity, A Univ Penn, Sch Med, Dept Radiat Oncol, Rm 195,John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA Univ Penn Rm 195,John Morgan Bldg,3620 Hamilton Walk Philadelphia PA USA 19104
Citazione:
C.H. Chen et al., "Regulation of glut1 mRNA by hypoxia-inducible factor-1 - Interaction between H-ras and hypoxia", J BIOL CHEM, 276(12), 2001, pp. 9519-9525

Abstract

Oncogenic transformation and hypoxia both induce glut1 mRNA, We studied the interaction between the ras oncogene and hypoxia in up-regulating glut1 mRNA levels using Rat1 fibroblasts transformed with H-ras (Rat1-ras), Transformation with H-ras led to a substantial increase in glut1 mRNA levels under normoxic conditions and additively increased glut1 mRNA levels in concertwith hypoxia. Using a luciferase reporter construct containing 6 kilobase pairs of the glut1 promoter, we showed that this effect was mediated at thetranscriptional level. Promoter activity was much higher in Rat1-ras cellsthan in Rat1 cells and could be down-regulated by cotransfection with a dominant negative Ras construct (RasN17). A 480-base pair (bp) cobalt/hypoxia-responsive fragment of the promoter containing a HIF-1 binding site showedsignificantly higher activity in Rat1-ras cells than in Rat1 cells, suggesting that Ras might mediate its effect through HIF-1 even under normoxic conditions. Consistent with this, Rat1-ras cells displayed higher levels of HIF1-alpha protein under normoxic conditions. In addition, a promoter construct containing a 4-bp mutation in the HIF1 binding site showed lower activity in Rat1 ras cells than a construct with an intact HIF1 binding site. Theactivity of the latter construct but not the former could be down-regulated by RasN17, supporting the importance of the HIF1 binding site in regulation by Ras, The phosphatidylinositol 3-kinase inhibitor LY29004 down-regulated glut1 promoter activity and mRNA levels under normoxia and also decreased HIF1 alpha protein levels in these cells. Collectively these results indicate that H-Ras up-regulates the glut1 promoter, at least in part, by increasing HIF-1 alpha protein levels leading to transactivation of promoter through the HIF-1 binding site.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 04:12:46