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Titolo:
Stable transfection of urokinase-type plasminogen activator antisense construct modulates invasion of human glioblastoma cells
Autore:
Mohanam, S; Jasti, SL; Kondraganti, SR; Chandrasekar, N; Kin, Y; Fuller, GN; Lakka, SS; Kyritsis, AP; Dinh, DH; Olivero, WC; Gujrati, M; Yung, WKA; Rao, JS;
Indirizzi:
Univ Illinois, Coll Med, Dept Biomed & Therapeut Sci, Div Canc Biol, Peoria, IL 61656 USA Univ Illinois Peoria IL USA 61656 ci, Div Canc Biol, Peoria, IL 61656 USA Univ Illinois, Coll Med, Dept Neurosurg, Peoria, IL 61656 USA Univ Illinois Peoria IL USA 61656 d, Dept Neurosurg, Peoria, IL 61656 USA Univ Illinois, Coll Med, Dept Pathol, Peoria, IL 61656 USA Univ Illinois Peoria IL USA 61656 Med, Dept Pathol, Peoria, IL 61656 USA Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 tr, Dept Neurosurg, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 r, Dept Neurooncol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Neuropathol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 , Dept Neuropathol, Houston, TX 77030 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 8, volume: 7, anno: 2001,
pagine: 2519 - 2526
SICI:
1078-0432(200108)7:8<2519:STOUPA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-BOUND UROKINASE; LEWIS LUNG-CARCINOMA; HUMAN OVARIAN-CANCER; HUMAN BRAIN-TUMORS; HUMAN GLIOMA-CELLS; IN-VITRO; GROWTH-FACTOR; MALIGNANT GLIOMA; RAT-BRAIN; INHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Rao, JS Univ Illinois, Coll Med, Dept Biomed & Therapeut Sci, Div Canc Biol, 1 Illini Dr,Box 1649, Peoria, IL 61656 USA Univ Illinois 1 Illini Dr,Box1649 Peoria IL USA 61656 L 61656 USA
Citazione:
S. Mohanam et al., "Stable transfection of urokinase-type plasminogen activator antisense construct modulates invasion of human glioblastoma cells", CLIN CANC R, 7(8), 2001, pp. 2519-2526

Abstract

The diffuse and extensive infiltration of malignant gliomas into the surrounding normal brain is believed to rely on modifications of the proteolysisof extracellular matrix components. A key molecule in regulating plasminogen-mediated extracellular proteolysis is the urokinase-type plasminogen activator (uPA). To investigate the role of uPA in the invasive process of brain tumors, we stably transfected a human glioblastoma cell line SNB19 with a vector capable of expressing an antisense transcript complementary to the1020 bases at the 3 ' end of the uPA cDNA. Parental, vector-, and antisense construct-stably transfected cell lines were analyzed for uPA mRNA transcript by Northern blot analysis, for uPA enzyme activity by zymography, and for uPA protein levels by Western blotting. The levels of uPA mRNA, protein, and enzyme activities were significantly lower in antisense clones than in parental and vector controls. Radioreceptor binding studies demonstrated that uPA receptor levels remained the same in parental, vector-, and antisense-transfected cells. The antisense-transfected cells showed a markedly lower level of invasion in the Matrigel invasion assays, and their spheroids failed to invade the fetal rat brain aggregates in the coculture system. Green fluorescent protein (GFP) expressing parental and antisense transfectants was generated for detection in mouse brain tissue without any posttreatment. Intracerebral injection of antisense stable transfectants significantly reduced tumor formation compared with that in controls. Our results suggested that down-regulation of uPA expression may be a feasible approach to reducing the malignancy and invasiveness of glial tumors.

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Documento generato il 07/07/20 alle ore 15:42:43