title: 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.
abstract: 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.
authors.affiliation: Department of Urology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Hannes
authors.initials: H
authors.lastname: Neuwirt
authors.forename: Martin
authors.initials: M
authors.lastname: Puhr
authors.forename: Frédéric R
authors.initials: FR
authors.lastname: Santer
authors.forename: Martin
authors.initials: M
authors.lastname: Susani
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Doppler
authors.forename: Gemma
authors.initials: G
authors.lastname: Marcias
authors.forename: Veronika
authors.initials: V
authors.lastname: Rauch
authors.forename: Maria
authors.initials: M
authors.lastname: Brugger
authors.forename: Alfred
authors.initials: A
authors.lastname: Hobisch
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig