Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer
Suppressor of cytokine signaling-3 antagonizes cAMP effects on proliferation and apoptosis and is expressed in human prostate cancer
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DOI：
10.2353/ajpath.2006.060171
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发表时间：
2006-12-01
影响因子：
6
通讯作者：
Culig, Zoran
中科院分区：
文献类型：
--
作者：
Bellezza, Ilaria;Neuwirt, Hannes;Culig, Zoran
白细胞介素-6水平在前列腺癌中升高，激活不同的信号转导途径，包括Janus激酶/信号转导器和转录激活器（STAT）3。然而，STAT3的磷酸化已被报道与细胞增殖的刺激或抑制作用有关。为了更好地了解STAT3在良性和恶性前列腺中的调控机制，我们研究了细胞因子信号传导抑制因子(SOCS)-3的作用。不表达磷酸化STAT3的细胞系被发现是socs -3阳性。去甲基化剂处理后，SOCS-3在LNCaP细胞中重新表达。SOCS-3免疫组化在良性区域呈阴性或弱反应，而在肿瘤组织中均有表达。为了研究SOCS-3在细胞事件调控中的作用，我们用cAMP衍生物培养癌细胞。该处理产生较高的SOCS-3水平，减少[H-3]胸腺嘧啶掺入，增加凋亡细胞的百分比。然而，通过短干扰RNA方法下调SOCS-3导致增殖抑制和凋亡率增加。总的来说，我们的研究结果表明，SOCS-3拮抗cAMP对细胞事件的调节，并在前列腺癌中表达。
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 [H-3]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 inhuman prostate cancer.