Abstract
To identify molecules to serve as diagnostic markers for high-grade prostate cancer (PC) and targets for novel therapeutic drugs, we investigated the gene expression profiles of high-grade PCs using a cDNA microarray combined with laser microbeam microdissection. We subsequently confirmed that the ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) was expressed exclusively in high-grade PCs with high Gleason scores. Semi-quantitative reverse transcription PCR and immunohistochemical analysis confirmed the overexpression of ISG15, a 165 amino acid interferon-inducible ubiquitin-like protein, specifically in high-grade PCs with high Gleason scores 8-9, while it was not expressed in the normal prostate. Immunohistochemical analysis using anti-ISG15 polyclonal antibody confirmed an elevated expression of ISG15 protein in high-grade PCs as well as low-grade PCs compared with that in normal prostate (NP) epithelium. Knockdown of ISG15 expression by short interfering RNA (siRNA) in a PC cell line resulted in marked attenuation of PC cell survival; concordantly, ISG15 overexpression in a PC cell line promoted PC cell growth, indicating its oncogenic property. These findings suggest that ISG15 is involved in cell growth and survival of PCs and that it could be a potential molecular target for new therapeutics and a diagnostic biomarker for human PCs.
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