Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma
Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma
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DOI：
10.1016/s1535-6108(04)00019-4
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发表时间：
2004-02-01
期刊：
影响因子：
50.3
通讯作者：
Staudt, LM
中科院分区：
文献类型：
--
作者：
Hurt, EM;Wiestner, A;Staudt, LM
癌基因c-maf在多发性骨髓瘤中的易位率为5%-10%。出乎意料的是，我们在缺乏c-maf易位的骨髓瘤细胞系和50%的多发性骨髓瘤骨髓样本中观察到c-maf表达。通过基因表达谱分析，我们确定了三个c-maf靶基因：细胞周期蛋白D2，整合素β 7和CCR 1。c-maf反式激活细胞周期蛋白D2启动子并增强骨髓瘤增殖，而c-maf的显性抑制阻断免疫缺陷小鼠中的肿瘤形成。c-maf驱动的整合素β 7的表达增强骨髓瘤与骨髓基质的粘附并增加VEGF的产生。我们认为c-maf通过刺激细胞周期进程和改变骨髓基质相互作用来转化浆细胞。骨髓瘤中c-maf的频繁过度表达使其成为治疗干预的有吸引力的靶点。
The oncogene c-maf is translocated in similar to5%-10% of multiple myelomas. Unexpectedly, we observed c-maf expression in myeloma cell lines lacking c-maf translocations and in 50% of multiple myeloma bone marrow samples. By gene expression profiling, we identified three c-maf target genes: cyclin D2, integrin beta7, and CCR1. c-maf transactivated the cyclin D2 promoter and enhanced myeloma proliferation, whereas dominant inhibition of c-maf blocked tumor formation in immunodeficient mice. c-maf-driven expression of integrin beta7 enhanced myeloma adhesion to bone marrow stroma and increased production of VEGF. We propose that c-maf transforms plasma cells by stimulating cell cycle progression and by altering bone marrow stromal interactions. The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention.