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Titolo:
Effect of an EGF-R selective tyrosine kinase inhibitor and an anti-androgen on LNCaP cells: Identification of divergent growth regulatory pathways
Autore:
Jones, HE; Barrow, D; Dutkowski, CM; Goddard, L; Smith, C; Harper, ME; Nicholson, RI;
Indirizzi:
Cardiff Univ, Welsh Sch Pharm, Tenovus Ctr Canc Res, Cardiff CF10 3XF, S Glam, Wales Cardiff Univ Cardiff S Glam Wales CF10 3XF ardiff CF10 3XF, S Glam, Wales
Titolo Testata:
PROSTATE
fascicolo: 1, volume: 49, anno: 2001,
pagine: 38 - 47
SICI:
0270-4137(20010915)49:1<38:EOAEST>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN PROSTATIC-CARCINOMA; FACTOR-ALPHA; RECEPTOR ACTIVATION; ESTROGEN-RECEPTOR; GENE-EXPRESSION; OVARIAN-CANCER; MESSENGER-RNA; BREAST-CANCER; LINE LNCAP; RESPONSES;
Keywords:
prostate cancer; tyrosine kinase; EGF-R;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Jones, HE Cardiff Univ, Welsh Sch Pharm, Tenovus Ctr Canc Res, Redwood Bldg, CardiffCF10 3XF, S Glam, Wales Cardiff Univ Redwood Bldg Cardiff S Glam Wales CF10 3XF m, Wales
Citazione:
H.E. Jones et al., "Effect of an EGF-R selective tyrosine kinase inhibitor and an anti-androgen on LNCaP cells: Identification of divergent growth regulatory pathways", PROSTATE, 49(1), 2001, pp. 38-47

Abstract

Background. The effect of an EGF-R selective tyrosine kinase (EGF-RTK) quinazoline inhibitor ZM252868 was determined on the androgen-sensitive human prostatic tumour cell line LNCaP which can also respond via the EGF-R-regulated growth pathway for cell proliferation. Potential interaction or 'cross-talk' between steroid and the growth factor mitogen-activated protein kinase (MAPK) signalling pathway was also investigated. Methods. The responses of LNCaP cells to various growth factors in the absence and presence of the EGF-RTK inhibitor and/or steroid and anti-androgenCasodex, was determined using cell population analysis. The effect of the inhibitor on the expression of androgen receptor, EGF-R and activated MAPK was assessed immunocytochemically and changes in the MAPK signalling cascade were also determined using Western blotting techniques. Results. The ZM252868 inhibitor had no effect on LNCaP basal growth. At 100 nM and 1 muM concentrations, the inhibitor reduced the marked EGF- and TGF-alpha -stimulated LNCaP cell growth by 60% and to basal levels, respectively. Both bFGF- and 5 alpha -DHT-stimulated growth were unaffected in this concentration range. The inhibitor (1 muM) decreased the expression of immunoreactive EGF-R but had no effect on androgen receptor levels. Activation of MAPK by EGF was noted, being down-regulated by the inhibitor at a concentration of 1 muM. MAPK was not activated by 5 alpha -DHT, The anti-androgenCasodex reduced 5 alpha -DHT-stimulated cell growth but had no effect on EGF-R mediated LNCaP growth or EGF-stimulated activated MAPK activity. Treatment with EGF and 5 alpha -DHT in combination produced an additive effect on cell proliferation, with the anti-androgen and the EGF-RTK inhibitor onlyreducing the 5 alpha -DHT- or EGF-stimulated portion of growth, respectively. Conclusions. The study demonstrated the efficacy and selectivity of the ZM252868 inhibitor in inhibiting EGF-R mediated LNCaP cell growth. Additionally, no interaction between androgen and EGF-R mediated growth pathways was determined. Prostate 49: 38-47,2001. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:21:31