Androgen receptors and hormone sensitivity of a human prostatic cancer cell line (PC-3) are modulated by natural beta-interferon

Sica, Gigliola; Dell'Acqua, Giorgio; Iacopino, Fortunata; Fattorossi, Andrea; Marchetti, Paolo; Kwast, Theodorus H. van der; Pavone‐Macaluso, M.

doi:10.1007/bf00431546

Cited by 21 publications

(23 citation statements)

References 19 publications

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“…On the basis of the pleiotropic activities of IFNs, some downstream mediators, however, may also trigger tumorigenesis, especially when the upregulation is uncoupled from complex IFN-induced responses. In PCa, IFNs not only inhibit the proliferation of PCa cells (Sica et al, 1994) but also upregulate the AR expression (Sica et al, 1994;Basrawala et al, 2006) known to exhibit growth-promoting effects (Stanbrough et al, 2001;Berger et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Expression, regulation and function of the ISGylation system in prostate cancer

et al. 2009

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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, ARdependent 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 þ androgensensitive 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.

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Section: Discussionmentioning

confidence: 99%

Expression, regulation and function of the ISGylation system in prostate cancer

et al. 2009

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“…IFN treatment of prostate cancer cells is known to inhibit cell proliferation (Sica et al, 1994;Kominsky et al, 2000). However, it is not known whether IFNtreatment of PrSCs results in inhibition of cell growth.…”

Section: Regulation Of Androgen Receptor Levels By Interferons Z Basrmentioning

confidence: 99%

“…Moreover, treatment of human prostate cancer cell line PC-3 with natural IFN-beta is known to increase AR protein levels (Sica et al, 1994). Therefore, we tested Figure 3 Treatment of PrSCs with IFN-alpha results in nuclear localization of AR.…”

Section: Regulation Of Androgen Receptor Levels By Interferons Z Basrmentioning

confidence: 99%

“…Both types of IFNs function through transcriptional activation of IFNactivatable genes encoding the IFN-inducible proteins that mediate the biological activities of IFNs. Importantly, treatment of human prostate cancer cell lines with the type I IFN (Sica et al, 1994) or the type II IFN (Kominsky et al, 2000) is known to inhibit cell growth. Additionally, treatment of human prostate cancer cell line PC-3 with natural IFN-beta is known to upregulate the AR protein levels (Sica et al, 1994).…”

mentioning

confidence: 99%

“…Importantly, treatment of human prostate cancer cell lines with the type I IFN (Sica et al, 1994) or the type II IFN (Kominsky et al, 2000) is known to inhibit cell growth. Additionally, treatment of human prostate cancer cell line PC-3 with natural IFN-beta is known to upregulate the AR protein levels (Sica et al, 1994). Notably, expression of a set of IFN-activatable genes is upregulated during the onset of cellular senescence in human PrECs (Untergasser et al, 2002).…”

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Androgen receptor levels are increased by interferons in human prostate stromal and epithelial cells

et al. 2005

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Proliferation of normal and malignant prostate epithelium is regulated by androgen stimulation via both the androgen receptor (AR)-positive stromal and epithelial cells. However, it is not known how AR expression is regulated in human prostate cells. We report that treatment of normal human prostate stromal cells (PrSCs) with type I IFN (alpha or beta), but not type II IFN (gamma), resulted in increased levels of AR protein. The maximal increase in AR protein levels was dependent on the dose and the duration of the IFN-alpha treatment. We found that the increase in AR protein levels was independent of de novo transcription and protein synthesis. Interestingly, the IFN-alpha treatment of PrSCs resulted in considerable nuclear accumulation of AR, stimulation of AR-mediated transcription of reporter genes, and retardation of cell proliferation. Furthermore, treatment of normal human prostate epithelial cells with IFNs (alpha, beta or gamma) also resulted in increased levels of AR protein. Together, our observations identify the androgen receptor as an IFN-regulated protein in normal human prostate stromal and epithelial cells and predict that IFN-induced levels of AR in prostate cells contribute to the regulation of androgen signaling.

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