Neuwirt H, Puhr M, Cavarretta I T, Mitterberger M, Hobisch A, Culig Z
Univ.-Klinik für Urologie, Medizinische Universität Innsbruck, Innsbruck, Osterreich.
Aktuelle Urol. 2009 Aug;40(4):231-4. doi: 10.1055/s-0028-1098887. Epub 2009 Jul 24.
Suppressors of cytokine signalling (SOCS) are induced by interleukins and peptide hormones. These molecules prevent the activation of diverse signalling pathways in benign and malignant cells. In previous studies, we showed that SOCS-3 is expressed in most prostate cancer cell lines and tissue specimens. In the present study we investigated the effects of androgen on the regulation of SOCS-3 in prostate cancer cell lines.
SOCS-3 expression was determined with PCR and Western blot techniques. The activity of the SOCS-3 promoter was measured with the luciferase test. We measured proliferation with (3)H-thymidine assay.
We show that androgen induces the expression of SOCS-3 in two prostate cancer cell lines. The non-steroidal anti-androgen bicalutamide is able to block the induction of SOCS-3 -expression. Androgenic hormones did not induce the expression of SOCS-3 mRNA or its promoter activity. In LNCaP-IL-6- cells transfected with the inducible Tet-On construct SOCS-3 expression was induced. The effects of androgenic hormones on the proliferation and induction of PSA were -diminished in the presence of SOCS-3.
Our results show that androgenic -regulation of SOCS-3 leads to inhibition of prolif-eration and secretion in human prostate cancer.
细胞因子信号转导抑制因子（SOCS）由白细胞介素和肽类激素诱导产生。这些分子可阻止良性和恶性细胞中多种信号通路的激活。在先前的研究中，我们发现SOCS-3在大多数前列腺癌细胞系和组织标本中均有表达。在本研究中，我们调查了雄激素对前列腺癌细胞系中SOCS-3调控的影响。
采用PCR和蛋白质印迹技术测定SOCS-3的表达。用荧光素酶试验检测SOCS-3启动子的活性。我们用³H-胸腺嘧啶核苷测定法测量细胞增殖。
我们发现雄激素可诱导两种前列腺癌细胞系中SOCS-3的表达。非甾体类抗雄激素比卡鲁胺能够阻断SOCS-3表达的诱导。雄激素类激素未诱导SOCS-3 mRNA的表达或其启动子活性。在用可诱导的Tet-On构建体转染的LNCaP-IL-6细胞中，SOCS-3表达被诱导。在存在SOCS-3的情况下，雄激素类激素对前列腺特异性抗原（PSA）增殖和诱导的影响减弱。
我们的结果表明，雄激素对SOCS-3的调控导致人前列腺癌增殖和分泌的抑制。
