The ubiquitin-like molecule interferon-stimulated gene 15 is overexpressed in human prostate cancer.
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.
Satake
Hirofumi
H
Department of Urology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan. jm-satakeh@kochi-u.ac.jp
Tamura
Kenji
K
Furihata
Mutsuo
M
Anchi
Takashi
T
Sakoda
Hatsune
H
Kawada
Chiaki
C
Iiyama
Tatsuo
T
Ashida
Shingo
S
Shuin
Taro
T
D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000737:chemistry*; D014452:Ubiquitins / Q000096:biosynthesis*
D016207:Cytokines; D025801:Ubiquitin; D014452:Ubiquitins; C074034:ISG15 protein, human