The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells
The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells
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DOI：
10.2353/ajpath.2006.050872
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发表时间：
2006-05-01
影响因子：
6
通讯作者：
Åman, P
中科院分区：
文献类型：
--
作者：
Engström, K;Willén, H;Åman, P
粘液类/圆形细胞脂肪肉瘤（MLS/RCLS）是脂肪肉瘤最常见的亚型。大多数MLS/RCL携带T（12; 16）易位，导致FUS-DDIT3融合基因。我们研究了FUS-DDIT3融合在MLS/RCLS在FUS-DDIT3-和DDIT3转染的人HT1080肉瘤细胞中的发展中的作用。表达FUS-DDIT3和DDIT3的细胞在严重组合的免疫缺陷型小鼠中随着脂肪肉瘤的形式生长，并表现出与MLS/RCL网络相似的毛细血管网络形态。基于微阵列的HT1080，转染的细胞以及MLS/RCLS衍生的细胞系的比较表明，FUS-DDIT3-和DDIT3转染的变体朝着MLS/RCLS样表达模式转移。 DDIT3转染的细胞通过脂肪的积累和转化为脂肪细胞样形态来对成脂因子反应。总之，由于融合癌基因FUS-DDIT3和正常DDIT3在原始肉瘤细胞系中表达时会诱导脂肪肉瘤表型，因此MLS/ RCLS可能会来自其他细胞类型以外的细胞类型。这可以解释MLS/RCL在非磷萨组织中的优先发生。此外，脂肪细胞和典型的MLS/RCLS毛细管网络的发展可能是融合癌基因的DDIT3转录因子合作伙伴的效果。
Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS-DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe combined immunodeficient mice and exhibited a capillary network morphology that was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/ RCLS may develop from cell types other than preadipocytes. This may explain the preferential occurrence of MLS/RCLS in nonadipose tissues. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene.