High activin A-expression in human neuroblastoma: suppression of malignant potential and correlation with favourable clinical outcome
High activin A-expression in human neuroblastoma: suppression of malignant potential and correlation with favourable clinical outcome
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DOI：
10.1038/sj.onc.1208087
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发表时间：
2005-01-20
期刊：
影响因子：
8
通讯作者：
Schweigerer, L
中科院分区：
文献类型：
--
作者：
Schramm, A;von Schuetz, V;Schweigerer, L
MYCN癌基因的扩增有助于人类神经母细胞瘤的恶性进展，但其机制仍不清楚。我们以前已经证明，N-Myc通过下调一种血管生成抑制剂（被鉴定为β-腺苷酸β A同二聚体激活素A）促进血管生成。在这里，我们试图定义激活素A在人神经母细胞瘤中表达的分子、生物学和临床后果。我们报告说，激活素A表达增强可以抑制体外扩增MYCN的人神经母细胞瘤细胞的增殖和集落形成;它可以抑制体内神经母细胞瘤的生长和血管生成;它在分化的人神经母细胞瘤中高度表达，但在未分化的人神经母细胞瘤中不高表达;它与神经母细胞瘤患者的良好结局相关。我们的研究结果表明，激活素A的高表达在人神经母细胞瘤中起着重要的有益作用。
Amplification of the MYCN oncogene contributes to the malignant progression of human neuroblastomas, but the mechanisms have remained unclear. We have previously demonstrated that N-Myc facilitates angiogenesis by downregulating an angiogenesis inhibitor identified as the inhibin betaA homodimer activin A. Here, we have sought to define the molecular, biological and clinical consequences of activin A expression in human neuroblastoma. We report that enhanced activin A expression suppresses proliferation and colony formation of human neuroblastoma cells with amplified MYCN in vitro; that it inhibits neuroblastoma growth and angiogenesis in vivo; that it is highly expressed in differentiated, but not undifferentiated human neuroblastomas; and that it correlates with favourable outcome of neuroblastoma patients. Our results indicate that high activin A expression plays an important beneficial role in human neuroblastoma.