許多研究人員假設(shè),，發(fā)生免疫反應(yīng)或讓身體對抗癌癥是一件好事,。但是根據(jù)加州大學(xué)圣地亞哥分校醫(yī)學(xué)院發(fā) 表的一項研究，卻強烈地建議,，發(fā)炎與腫瘤惡化有關(guān),，而且在攝護腺癌的轉(zhuǎn)移中，扮演著重要的角色。
在利用小鼠模型并且在人類組織證實的研究中,，科學(xué)家觀察到一種名為IkB kinasea (IKKa)的蛋白激酶,，IKKa會關(guān)閉一種名為Maspin的基因表現(xiàn)。
maspin基因是一種腫瘤抑制基因,，其產(chǎn)物是絲胺酸蛋白酶抑制劑,，在細胞的遷徙、運動和增生中起重要作用,，并且能抑制腫瘤的發(fā)生和發(fā)展。已知這個基因具有對抗乳房和攝護腺癌轉(zhuǎn)移的活性,。
研究人員發(fā)現(xiàn)Maspin 的生產(chǎn),，會被一系列由腫瘤發(fā)炎細胞引起的事件所抑制，最后導(dǎo)致攝護腺癌細胞轉(zhuǎn)移,。這項研究發(fā)表于3月19 日的Nature的網(wǎng)絡(luò)版中,，研究作者Michael Karin辨認出引起攝護腺癌發(fā)展末期階段之轉(zhuǎn)移的機制。這項研究也有助于研發(fā)對抗癌癥轉(zhuǎn)移的療法,。
(資料來源 : 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: [email protected]).
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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.
