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Titolo:
Antitumor effect of an HER2-specific antibody-toxin fusion protein on human prostate cancer cells
Autore:
Wang, L; Liu, BL; Schmidt, M; Lu, Y; Wels, W; Fan, Z;
Indirizzi:
Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 ept Expt Therapeut, Houston, TX 77030 USA Chemotherapeut Forschungsinst, Frankfurt, Germany Chemotherapeut Forschungsinst Frankfurt Germany nst, Frankfurt, Germany
Titolo Testata:
PROSTATE
fascicolo: 1, volume: 47, anno: 2001,
pagine: 21 - 28
SICI:
0270-4137(20010401)47:1<21:AEOAHA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPIDERMAL GROWTH-FACTOR; GENE AMPLIFICATION STATUS; IN-SITU HYBRIDIZATION; FACTOR RECEPTOR; DIPHTHERIA-TOXIN; TYROSINE KINASE; NEU ONCOGENE; FACTOR-ALPHA; PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY;
Keywords:
HER2; prostate cancer; apoptosis; immunotoxin; recombinant fusion protein; dihydrotestosterone;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Fan, Z Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, 1515 Holcombe Blvd,Houston, TX 77030 USA Univ Texas 1515 Holcombe Blvd Houston TX USA 77030 on, TX 77030 USA
Citazione:
L. Wang et al., "Antitumor effect of an HER2-specific antibody-toxin fusion protein on human prostate cancer cells", PROSTATE, 47(1), 2001, pp. 21-28

Abstract

BACKGROUND. HER2/neu has been implicated in the oncogenesis of human prostate cancer. Clinical studies have suggested that overexpression of HER2 maybe one of the indicators of poor prognosis in prostate cancer patients. METHODS. We used Western blot analysis to examine the expression of HER2 in a panel of established human prostate cancer cell lines and used an MTT assay to evaluate the cytotoxicity on these cells of a recombinant fusion protein consisting of an HER2-specific single-chain antibody and the Pseudomonas exotoxin A, scFv(FRP5)-ETA. RESULTS. LNCaP cells express high levels of HER2 protein. Exposure of LNCaP cells to scFv(FRP5)-ETA caused remarkable cell death. In contrast, PC3M cells, which express an undetectable level of HER2 protein, were resistant to scFv(FRP5)-ETA-induced cytotoxicity. MDA PCa 2a, MDA PCa 2b, and DU145 cells express low-to-medium levels of HER2 protein and showed an HER2 level-dependent response to scFv(FRP5)-ETA-induced cytotoxicity. The scFv(FRP5)-ETA-induced cytotoxicity of LNCaP cells could be inhibited by an anti-HER2 monoclonal antibody (mAb), which downregulated the levels of HER2 protein, indicating the specificity of scFv(FRP5)-ETA in inducing cytotoxicity in LNCaP cells. Using an apoptosis ELISA, we demonstrated that scFv(FRP5)-ETA induced apoptosis in LNCaP cells. The apoptosis was inhibited by the presence of dihydrotestosterone (DHT) in culture medium. Exposure of LNCaP cells to scFv(FRP5)-ETA caused reduction in the level of the prostate-specific antigen (PSA). CONCLUSIONS. Our data suggest that scFv(FRP5)-ETA might be a useful agent for the treatment of human prostate cancer cells with high levels of HER2 expression. Prostate 47: 21-28, 2001. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 10:22:18