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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
2009-7-20
pubmed:abstractText
The androgen receptor (AR) plays a crucial role in the modulation of prostate cell proliferation and is involved in the development and progression of prostate cancer (PCa). An understanding of the complex regulation of AR provides novel treatment options for PCa. Here, we show (i) that the ubiquitin-like modifier, interferon-stimulated gene 15 (ISG15), and most enzymes involved in ISG15 conjugation were upregulated in tumor samples versus in non-malignant tissues of PCa patients and (ii) that the expression of these components significantly differed between tumors in patients treated with and without androgen ablation. Using PCa cell lines as in vitro models, the specific androgen-mediated, AR-dependent regulation of the ISGylation components was confirmed. In addition, the ISGylation system controls AR mRNA and protein expressions, as overexpression of Ube1L as a limiting ISGylation factor in the AR(+) androgen-sensitive PCa cell line, LNCaP, results in significant AR upregulation, accompanied by an increased proliferation even under androgen deprivation. Accordingly, Ube1L knockdown decreased the AR expression. Thus, this study describes for the first time the modulation of AR expression by ISGylation components, which affects the proliferation of PCa cells, thereby providing evidence for a novel function of the ISGylation system in malignant transformation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2606-20
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Expression, regulation and function of the ISGylation system in prostate cancer.
pubmed:affiliation
Medical Faculty, Institute for Medical Immunology, Martin-Luther-University Halle-Wittenberg, Halle, Germany. Andrea.Kiessling@novartis.com
pubmed:publicationType
Journal Article