Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Relation of vascular endothelial growth factor production to expression and regulation of hypoxia-inducible factor-1 alpha and hypoxia-inducible factor-2 alpha in human bladder tumors and cell lines
Autore:
Jones, A; Fujiyama, C; Blanche, C; Moore, JW; Fuggle, S; Cranston, D; Bicknell, R; Harris, AL;
Indirizzi:
John Radcliffe Hosp, Inst Mol Med, Imperial Canc Res Fund, Mol Oncol Unit,Oxford OX3 9DS, England John Radcliffe Hosp Oxford England OX3 9DS Unit,Oxford OX3 9DS, England Churchill Hosp, Dept Urol, Oxford OX3 7LJ, England Churchill Hosp OxfordEngland OX3 7LJ Dept Urol, Oxford OX3 7LJ, England Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Oxford OX3 9DU, England Univ Oxford Oxford England OX3 9DU ld Dept Surg, Oxford OX3 9DU, England
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 5, volume: 7, anno: 2001,
pagine: 1263 - 1272
SICI:
1078-0432(200105)7:5<1263:ROVEGF>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
RNASE PROTECTION ASSAY; HUMAN PROSTATE-CANCER; MESSENGER-RNA; IN-VIVO; GENE-EXPRESSION; CARCINOMA-CELLS; FACTOR 1-ALPHA; DEPENDENT REGULATION; SOLID TUMORS; ANGIOGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Harris, AL John Radcliffe Hosp, Inst Mol Med, Imperial Canc Res Fund, Mol Oncol Unit,Oxford OX3 9DS, England John Radcliffe Hosp Oxford England OX39DS d OX3 9DS, England
Citazione:
A. Jones et al., "Relation of vascular endothelial growth factor production to expression and regulation of hypoxia-inducible factor-1 alpha and hypoxia-inducible factor-2 alpha in human bladder tumors and cell lines", CLIN CANC R, 7(5), 2001, pp. 1263-1272

Abstract

Hypoxia is an important regulator of vascular endothelial growth factor (VEGF) expression, and VEGF is associated with poor prognosis in bladder cancer. To investigate further the mechanisms of VEGF regulation, we examined VEGF expression by mRNA and protein analysis in four human bladder cancer cell lines, shelving a progression from well to poorly differentiated phenotypes under varying conditions of confluence and hypoxia (0.1% O-2) and with chemical mimic of hypoxia, Hypoxia significantly increased VEGF protein expression in all cell lines, although this effect was dependent on the degreeof confluence. The superficial bladder cancer cell line RT4 lost hypoxia inducibility at confluence, whereas inducibility was maintained in the invasive cell lines 253J and EJ28, This pattern of VEGF expression in the invasive cell Lines correlated with the expression of the transcription factor hypoxia inducible factor-1 alpha (HIF-1 alpha) and with hypoxia-inducible factor-2 alpha. (HIF-2 alpha) and in RT4 correlated with a marked reduction inHIF-1 alpha inducibility at confluence. Using the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor LY 294002, we show that this VEGF hypoxia-inducible pathway regulated by HIF-1 alpha is distinct from a PI 3-kinase-dependent pathway, which regulates basal amounts of VEGF, but does not affect inducibility, Both HIF-1 alpha and HIF-2 alpha protein and mRNA were up-regulated in primary human bladder tumors (n = 12) compared with normal bladderspecimens (n = 4), with significant intertumor variation. These results suggest that components of the hypoxia response pathway, including HIF-1 alpha and HIF-2 alpha, are important cofactors in the regulation of VEGF in bladder cancer and are therapeutic targets in this disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 21:04:42