Central Lab, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Mol Immunol. 2011 Oct;49(1-2):8-17. doi: 10.1016/j.molimm.2011.07.013.
Dysregulation of Maspin expression and constitutive activation of NF-κB subunits are important events in tumorigenesis of prostate cancer. Recent finding points that RelB, which contributes to the alternative NF-κB activity, interferes with carcinogenesis in the prostate. We report here, that both the classical and the alternative NF-κB activities are constitutively present in androgen-insensitive human prostate cancer cells. Maspin and RelB expression is correlated negatively in prostate cancer tissues at the later stage. TNF-α signaling triggers the nuclear accumulation of RelB and the concomitant reduction of Maspin expression in a time-dependent manner. In addition, the proteasome inhibitor-induced Maspin expression is accompanied by the reduction of RelB expression. A successful depletion of RelB expression, but not RelA expression, induces Maspin expression. RelB-deficiency abrogates the proteasome inhibitor-induced Maspin expression. Moreover, we demonstrate that the enforced expression of RelB protein in prostate cancer cells inhibits Maspin expression. We propose that RelB is an essential molecule controlling the endogenous and the proteasome inhibitor-induced Maspin expression. Developing a RelB-targeted therapeutic intervention, which might be coupled with the induction of a tumor suppressor Maspin, is valuable in treating advanced, metastatic prostate cancer.
Maspin 表达失调和 NF-κB 亚基的组成性激活是前列腺癌发生肿瘤的重要事件。最近的研究结果表明，有助于替代 NF-κB 活性的 RelB 会干扰前列腺的癌变。我们在此报告，经典和替代的 NF-κB 活性在雄激素不敏感的人前列腺癌细胞中持续存在。Maspin 和 RelB 的表达在前列腺癌组织的晚期呈负相关。TNF-α 信号以时间依赖性方式触发 RelB 的核积累和伴随的 Maspin 表达减少。此外，蛋白酶体抑制剂诱导的 Maspin 表达伴随着 RelB 表达的减少。成功耗尽 RelB 表达，但不耗尽 RelA 表达，可诱导 Maspin 表达。RelB 缺陷可消除蛋白酶体抑制剂诱导的 Maspin 表达。此外，我们证明在前列腺癌细胞中强制表达 RelB 蛋白可抑制 Maspin 表达。我们提出 RelB 是控制内源性和蛋白酶体抑制剂诱导的 Maspin 表达的必需分子。开发针对 RelB 的治疗干预措施，可能与诱导肿瘤抑制因子 Maspin 相结合，对于治疗晚期转移性前列腺癌具有重要价值。
