Francesco Pierconti and Maurizio Martini equally contributed to this work.
Epigenetic silencing of SOCS3 identifies a subset of prostate cancer with an aggressive behavior†
Article first published online: 17 AUG 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 71, Issue 3, pages 318–325, 15 February 2011
How to Cite
Pierconti, F., Martini, M., Pinto, F., Cenci, T., Capodimonti, S., Calarco, A., Bassi, P. F. and Larocca, L. M. (2011), Epigenetic silencing of SOCS3 identifies a subset of prostate cancer with an aggressive behavior. Prostate, 71: 318–325. doi: 10.1002/pros.21245
- Issue published online: 20 JAN 2011
- Article first published online: 17 AUG 2010
- Manuscript Accepted: 12 JUL 2010
- Manuscript Received: 7 APR 2010
- Fondi d'Ateneo, Progetti (Università Cattolica, Rome, Italy). Grant Number: D1 2007-2008/2008-2009
- promoter hypermethylation;
- prostate cancer
Chronic inflammation and subsequent tissutal alterations may play a key role in prostate carcinogenesis. In this way, molecular alterations of the suppressor of cytokine signaling 3 (SOCS3), one of the most important inhibitory molecule of inflammatory signal transduction circuitries, could contribute to explain the pleiotropic role of interleukin-6 (IL-6) in this type of cancer.
We analyzed the methylation status and mRNA expression of SOCS3 in 20 benign prostate hyperplasias (BPH) and in 51 prostate cancer specimens. We analyzed the SOCS3 methylation status using methylation-specific PCR. Hypermethylation was confirmed by sequencing after subcloning. Epigenetic silencing of this gene was also demonstrated by real-time PCR and by immunohistochemestry. Results and correlation with clinical data were statistically analyzed.
We found that the promoter of SOCS3 was methylated in 39.2% of prostate cancer. On the contrary, all BPH and normal controls had an unmethylated pattern. Real-time analysis showed that in methylated cases SOCS3 mRNA expression was reduced by three and four folds as compared to BPH and unmethylated cases, respectively. Interestingly, SOCS3 mRNA level was higher in unmethylated prostate cancer than in BPH. The immunohistochemical staining analysis for SOCS 3 confirmed mRNA results. Moreover, methylation of SOCS3 promoter significantly associated with intermediate–high grade Gleason score (P = 0.0007) and with an unfavorable clinical outcome (P = 0.0019).
Our data suggest that SOCS3 hypermethylation may be involved in the pathogenesis of prostate cancer and could identify a tumor subset with an aggressive behavior. Prostate 71:318–325, 2011. © 2010 Wiley-Liss, Inc.