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Originally published online as doi:10.2353/ajpath.2009.080751 on March 26, 2009

Published online before print March 26, 2009
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(American Journal of Pathology. 2009;174:1921-1930.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080751

Suppressor of Cytokine Signaling (SOCS)-1 Is Expressed in Human Prostate Cancer and Exerts Growth-Inhibitory Function through Down-Regulation of Cyclins and Cyclin-Dependent Kinases

Hannes Neuwirt*, Martin Puhr*, Frédéric R. Santer*, Martin Susani{dagger}, Wolfgang Doppler{ddagger}, Gemma Marcias*, Veronika Rauch*, Maria Brugger*, Alfred Hobisch§, Lukas Kenner{dagger} and Zoran Culig*

From the Department of Urology* and Division of Biological Chemistry,{ddagger} Biocenter, Innsbruck Medical University, Innsbruck; the Institute of Clinical Pathology,{dagger} Medical University of Vienna, Vienna; the Department of Urology,§ General Hospital Feldkirch, Feldkirch; and the Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria

Suppressor of cytokine signaling (SOCS) proteins play a pivotal role in the development and progression of various cancers. We have previously shown that SOCS-3 is expressed in prostate cancer, and its expression is inversely correlated with activation of signal transducer and activator of transcription factor 3. We hypothesized that SOCS-1, if expressed in prostate cancer cells, has a growth-regulatory role in this malignancy. The presence of both SOCS-1 mRNA and protein was detected in all tested cell lines. To assess SOCS-1 expression levels in vivo, we analyzed tissue microarrays and found a high percentage of positive cells in both prostate intraepithelial neoplasias and cancers. SOCS-1 expression levels decreased in samples taken from patients undergoing hormonal therapy but increased in specimens from patients who failed therapy. In LNCaP-interleukin-6– prostate cancer cells, SOCS-1 was up-regulated by interleukin-6 and in PC3-AR cells by androgens; such up-regulation was also found to significantly impair cell proliferation. To corroborate these findings, we used a specific small interfering RNA against SOCS-1 and blocked expression of the protein. Down-regulation of SOCS-1 expression caused a potent growth stimulation of PC3, DU-145, and LNCaP-interleukin-6– cells that was associated with the increased expression levels of cyclins D1 and E as well as cyclin-dependent kinases 2 and 4. In summary, we show that SOCS-1 is expressed in prostate cancer both in vitro and in vivo and acts as a negative growth regulator.


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