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Titolo:
Androgen stimulated cellular proliferation in the human prostate cancer cell line LNCaP is associated with reduced retinoblastoma protein expression
Autore:
Taneja, SS; Ha, S; Garabedian, MJ;
Indirizzi:
NYU, Sch Med, Dept Urol, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA NYU New York NY USA 10016 lan Comprehens Canc Ctr, New York, NY 10016 USA NYU, Sch Med, Dept Microbiol, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA NYU New York NY USA 10016 lan Comprehens Canc Ctr, New York, NY 10016 USA
Titolo Testata:
JOURNAL OF CELLULAR BIOCHEMISTRY
fascicolo: 1, volume: 84, anno: 2002,
pagine: 188 - 200
SICI:
0730-2312(2002)84:1<188:ASCPIT>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
STEROID BINDING CHARACTERISTICS; TUMOR-SUPPRESSOR PROTEIN; RECEPTOR GENE; TRANSCRIPTIONAL ACTIVATION; ENDOCRINE-THERAPY; CYCLE ARREST; CARCINOMA; PHOSPHORYLATION; PATHWAY; GROWTH;
Keywords:
retinoblastoma protein; androgen; prostate cancer; cell cycle; ubiquitination; 26S proteasome;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Taneja, SS NYU, Sch Med, Dept Urol, Kaplan Comprehens Canc Ctr, 540 1st Ave, New York, NY 10016 USA NYU 540 1st Ave New York NY USA 10016 e, New York, NY 10016 USA
Citazione:
S.S. Taneja et al., "Androgen stimulated cellular proliferation in the human prostate cancer cell line LNCaP is associated with reduced retinoblastoma protein expression", J CELL BIOC, 84(1), 2002, pp. 188-200

Abstract

To elucidate the mech an ism of androgen-dependent cellular proliferation in prostate cancer, androgen dependent alterations of individual cell cycleregulatory proteins in the androgen-sensitive prostate cancer cell line LNCaP were evaluated. LNCaP cells were deprived of androgens by culture in steroid-depleted media for 5 days, which resulted in the maximal accumulationof cells in G(0)/G(1) phase of the cell cycle. The mitogenic concentrationof the synthetic androgen R1881 was established as 0.1 nM using cell proliferation assay. Protein and mRNA levels of particular cyclins, cyclin-dependent kinases (Cdks), cyclin-dependent kinase inhibitors (Ckis), and the retinoblastoma proteins (Rb) were assessed. Androgen stimulation resulted in apost-transcriptional reduction in Rb protein levels, an increase in Rb phosphorylation at serine 780 and an accumulation of high molecular weight Rb protein species. Androgen stimulation also induced the expression of the Cdk2 and Cdk1 as well as their regulatory partners, cyclin A and cyclin B, resulting in a corresponding increase in cyclin A/Cdk2 activity in vitro. Pulse-chase showed decreased Rb protein stability in androgen-treated LNCaP cells. Collectively, our findings suggest a novel mechanism of androgen-dependent prostate cancer growth in which androgen stimulation results in decreased Rb protein expression in LNCaP cells. The observation of decreased Rb protein stability in the setting of increased phosphorylation supports the concept of phosphorylation mediated protein degradation. We propose that theobserved reduction in Rb protein level occurs through Rb degradation via the ubiquitin/proteasome pathway, and is preceded by selective Rb phosphorylation by cyclin A/Cdk2 and cyclin B/Cdk1. (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 02:08:02