Nature：炎症与摄护腺癌转移有关
许多研究人员假设，发生免疫反应或让身体对抗癌症是一件好事。但是根据加州大学圣地亚哥分校医学院发 表的一项研究，却强烈地建议，发炎与肿瘤恶化有关，而且在摄护腺癌的转移中，扮演着重要的角色。
在利用小鼠模型并且在人类组织证实的研究中，科学家观察到一种名为IkB kinasea (IKKa)的蛋白激酶，IKKa会关闭一种名为Maspin的基因表现。
maspin基因是一种肿瘤抑制基因，其产物是丝胺酸蛋白酶抑制剂，在细胞的迁徙、运动和增生中起重要作用，并且能抑制肿瘤的发生和发展。已知这个基因具有对抗乳房和摄护腺癌转移的活性。
研究人员发现Maspin 的生产，会被一系列由肿瘤发炎细胞引起的事件所抑制，最后导致摄护腺癌细胞转移。这项研究发表于3月19 日的Nature的网络版中，研究作者Michael Karin辨认出引起摄护腺癌发展末期阶段之转移的机制。这项研究也有助于研发对抗癌症转移的疗法。
(资料来源 : Bio.com)
部分英文原文：
Nature advance online publication 18 March 2007 | doi:10.1038/nature05656; Received 5 December 2006; Accepted 2 February 2007; Published online 18 March 2007
Nuclear cytokine-activated IKK
controls prostate cancer metastasis by repressing Maspin
Jun-Li Luo1, Wei Tan1, Jill M. Ricono2, Olexandr Korchynskyi1, Ming Zhang3, Steven L. Gonias2, David A. Cheresh2 & Michael Karin1
- Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
- Department of Pathology and the Moores Cancer Center, University of California, San Diego, La Jolla, California 92093-0803, USA
- Baylor College of Medicine, Department of Molecular and Cellular Biology, One Baylor Plaza, Houston, Texas 77030, USA
Correspondence to: Michael Karin1 Correspondence and requests for materials should be addressed to M.K. (Email: karinoffice@ucsd.edu).
Inflammation enhances tumour promotion through NF-
B-dependent mechanisms1. NF-B was also proposed to promote metastatogenesis through epithelial–mesenchymal transition2. Yet a mechanistic link between inflammation and metastasis is missing. We identified a role for IB kinase 
(IKK), activated by receptor activator of NF-B (RANK/TNFRSF11A), in mammary epithelial proliferation during pregnancy3. Owing to similarities between mammary and prostate epithelia, we examined IKK involvement in prostate cancer and its progression. Here we show that a mutation that prevents IKK activation slows down CaP growth and inhibits metastatogenesis in TRAMP mice, which express SV40 T antigen in the prostate epithelium4. Decreased metastasis correlated with elevated expression of the metastasis suppressor Maspin5, the ablation of which restored metastatic activity. IKK activation by RANK ligand (RANKL/TNFSF11) inhibits Maspin expression in prostate epithelial cells, whereas repression of Maspin transcription requires nuclear translocation of active IKK. The amount of active nuclear IKK in mouse and human prostate cancer correlates with metastatic progression, reduced Maspin expression and infiltration of prostate tumours with RANKL-expressing inflammatory cells. We propose that tumour-infiltrating RANKL-expressing cells lead to nuclear IKK activation and inhibition of Maspin transcription, thereby promoting the metastatic phenotype.
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