Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma
Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma
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DOI：
10.1016/s0002-9440(10)63940-5
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发表时间：
2001-01-01
影响因子：
6
通讯作者：
Savarese, TM
中科院分区：
文献类型：
--
作者：
Campbell, CL;Jiang, Z;Savarese, TM
先前的研究表明，IL-6 是 JAK-STAT 激活细胞因子家族的成员，在前列腺癌中发挥着重要作用。在这里，我们证明了该细胞因子家族的另一个成员白细胞介素 11 (IL-11) 及其受体成分（白细胞介素 11 受体；IL-11R），即 IL-11R α（参与配体识别）和 gp130（参与信号转导）在培养的正常和恶性前列腺来源的上皮细胞系中的共表达。在 DU-145 前列腺癌细胞系中，rhIL-11 刺激酪氨酸 705 磷酸化活性形式 STAT3 (STAT3 P-Tyr705) 短暂且剂量依赖性增加，参与 IL-11R 和 gp130 依赖性受体其他成员的下游信号传导。鉴于最近的数据表明组成型激活的 STAT3 可能与恶性表型相关，IL-11 在前列腺来源的细胞中激活 STAT3 的能力可能在机制上很重要。在来自正常前列腺、良性前列腺增生和前列腺癌的51个人类原发组织中，IL-11Rα和gp130普遍表达，其中IL-11Rα在前列腺癌中的表达显着升高。此外，与非恶性样本相比，酪氨酸磷酸化、活化形式的 STAT3 在恶性腺体细胞核中更为明显。因此，IL-11 受体系统在前列腺癌中上调，并且可能是在这些组织中维持 STAT3 活化形式的细胞因子网络的一部分。
Previous investigations have shown that interleukin-6, a member of the JAK-STAT activating family of cytokines, plays an important role in prostate carcinoma. Here we demonstrate the co-expression of another member of this cytokine family, interleukin-11 (IL-11), and components of its receptor (interleukin-11 receptor; IL-11R), ie, IL-11R alpha (involved in ligand recognition), and gp130 (involved in signal transduction) in cultured normal and malignant prostate-derived epithelial cell lines. In the DU-145 prostate carcinoma cell line, rhIL-11 stimulates a transient and dose-dependent increase in the tyrosine 705-phosphorylated, active form of STAT3 (STAT3 P-Tyr705), involved in the downstream signaling of IL-11R and other members of the gp130-dependent receptors. The ability of IL-11 to activate STAT3 in prostate-derived cells may be mechanistically important, given recent data suggesting that constitutively activated STAT3 may be associated with the malignant phenotype. In 51 human primary tissues derived from normal prostate, benign prostatic hyperplasia, and prostate carcinomas, IL-11R alpha and gp130 were commonly expressed, with a statistically significant elevation in the expression of IL-11R alpha in prostate carcinoma. Also, the tyrosine-phosphorylated, activated form of STAT3 was observed more prominently in the nuclei of cells residing in malignant glands compared to those in nonmalignant samples. Thus, the IL-11 receptor system is up-regulated in prostate carcinoma, and may be one part of a cytokine network that maintains STAT3 in its activated form in these tissues.