Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer.
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.
Bellezza
Ilaria
I
Department of Urology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, and Department of Pathology, General Hospital Feldkirch, Austria.
Neuwirt
Hannes
H
Nemes
Constanze
C
Cavarretta
Ilaria T
IT
Puhr
Martin
M
Steiner
Hannes
H
Minelli
Alba
A
Bartsch
Georg
G
Offner
Felix
F
Hobisch
Alfred
A
Doppler
Wolfgang
W
Culig
Zoran
Z
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D008745:Methylation; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D007377:Interleukin-3; D034741:RNA, Small Interfering; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000242:Cyclic AMP; D053612:Janus Kinases