A multigenic program mediating breast cancer metastasis to bone
A multigenic program mediating breast cancer metastasis to bone
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DOI：
10.1016/s1535-6108(03)00132-6
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发表时间：
2003-06-01
期刊：
影响因子：
50.3
通讯作者：
Massagué, J
中科院分区：
文献类型：
--
作者：
Kang, YB;Siegel, PM;Massagué, J
我们通过选择转移活性升高的人乳腺癌细胞系亚群，并在功能上验证这些细胞中过表达的基因，研究了溶骨性骨转移的分子基础。这些基因协同作用导致溶骨性转移，其中大多数编码分泌蛋白和细胞表面蛋白。这些基因中的两个，白细胞介素-11和CTGF，编码溶骨性和血管生成因子，其表达通过促转移细胞因子TGF β进一步增加。这种骨转移基因集的过表达叠加在亲代乳腺癌人群中已经存在的预后不良基因表达特征上，表明转移需要一组超出原发性肿瘤出现基础的功能。
We investigated the molecular basis for osteolytic bone metastasis by selecting human breast cancer cell line subpopulations with elevated metastatic activity and functionally validating genes that are overexpressed in these cells. These genes act cooperatively to cause osteolytic metastasis, and most of them encode secreted and cell surface proteins. Two of these genes, interleukin-11 and CTGF, encode osteolytic and angiogenic factors whose expression is further increased by the prometastatic cytokine TGFbeta. Overexpression of this bone metastasis gene set is superimposed on a poor-prognosis gene expression signature already present in the parental breast cancer population, suggesting that metastasis requires a set of functions beyond those underlying the emergence of the primary tumor.