Role of MxA in Human Prostate Cancer

我们比较了两种人前列腺癌细胞系PC-3的基因表达谱， 以及一种转移性更强的PC-3衍生物PC-3 M。我们发现MxA基因 在PC-3中表达为mRNA和蛋白质，但在其更具转移性的子系PC-3 M中不表达。我们 MxA在PC-3 M细胞和LOX（一种高转移性人黑素瘤细胞）中的表达上调 线，并发现他们的运动和入侵大大削减在体外和 PC-3 M在免疫功能低下小鼠的异种移植物中的转移能力显著降低。 一组药物的筛选显示，PC-3 M中的MxA表达可以通过以下方式增加： 几个小分子，这是伴随着细胞运动性下降。进一步 对这一调查路线的改进可能会产生一种新的发展战略， 抗转移治疗。大约50%的人前列腺癌表现出以下融合： 21号染色体上的两个基因TMPRS 2和ERG。这种融合通常与 侵袭性表型，并且基因融合导致 编码MxA家族基因Mx 1和Mx2的21号染色体。我们假设， Mx 1/2的表达是肿瘤侵袭性增加的原因， 基因型

We compared the gene expression profile of two human prostate cancer cell lines, PC-3 and a more metastatic derivative of PC-3 called PC-3M. We discovered that the MxA gene was expressed as mRNA and protein in PC-3 but not in its more metastatic daughter line, PC-3M. We upregulated MxA expression in PC-3M cells and in LOX, a highly metastatic human melanoma cell line, and found that their motility and invasion were drastically curtailed in vitro and the metastatic ability of PC-3M was significantly reduced in xenografts in immunocompromisd mice. A screen with a panel of drugs showed that MxA expression in PC-3M could be increased by several small molecules, and this was accompanied by a decrease in cell motility. Further refinements of this line of inquiry might result in a new strategy for development of antimetastasis therapeutics. Approximately 50% of human prostate cancers exhibit a fusion of two genes on chromosome 21, TMPRS2 and ERG. This fusion is commonly associated with an invasive phenotype, and the gene fusion results in an interstitial deletion of that portion of chromosome 21 that encodes the MxA family genes, Mx1 and Mx2. We postulate that the loss of expression of Mx1/2 is responsible for the increased aggrssiveness of tumors with this genotype.