Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer

Ilaria Bellezza, Hannes Neuwirt, Constanze Nemes, Ilaria T. Cavarretta, Martin Puhr, Hannes Steiner, Alba Minelli, Georg Bartsch, Felix Offner, Alfred Hobisch, Wolfgang Doppler, Zoran Culig

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Abstract

Interleukin-6, levels of which are elevated in prostate cancer, activates different signal transduction pathways including that of Janus kinases/signal transducer and activator of transcription (STAT)3. However, phosphorylation of STAT3 has been reported to be associated with either stimulatory or inhibitory effects on cellular proliferation. To better understand the mechanisms of STAT3 regulation in benign and malignant prostate, we have investigated the role of suppressor of cytokine signaling (SOCS)-3. Cell lines that did not express phosphorylated STAT3 were found to be SOCS-3-positive. SOCS-3 was re-expressed in LNCaP cells after treatment with a demethylating agent. SOCS-3 immunohistochemistry revealed a negative or weak reaction in benign areas, whereas its expression was detected in tumor tissue. To investigate the involvement of SOCS-3 in regulation of cellular events, we incubated cancer cells with a cAMP derivative. This treatment yielded higher SOCS-3 levels , reduced [3H]thymidine incorporation, and increased percentage of apoptotic cells. However, down-regulation of SOCS-3 by a short interfering RNA approach resulted in inhibition of proliferation and an increased apoptotic rate. Collectively , our results show that SOCS-3 antagonizes regulation of cellular events by cAMP and is expressed in human prostate cancer.

Original languageEnglish
Pages (from-to)2199-2208
Number of pages10
JournalAmerican Journal of Pathology
Volume169
Issue number6
DOIs
Publication statusPublished - Dec 2006

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Bellezza, I., Neuwirt, H., Nemes, C., Cavarretta, I. T., Puhr, M., Steiner, H., Minelli, A., Bartsch, G., Offner, F., Hobisch, A., Doppler, W., & Culig, Z. (2006). Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer. American Journal of Pathology, 169(6), 2199-2208. https://doi.org/10.2353/ajpath.2006.060171