c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme
c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme
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DOI：
10.1002/path.2564
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发表时间：
2009-07-01
影响因子：
7.3
通讯作者：
Fletcher, Christopher D. M.
中科院分区：
文献类型：
--
作者：
Snyder, Eric L.;Sandstrom, Deborah J.;Fletcher, Christopher D. M.
c-Jun及其上游激酶的基因组扩增被认为是从分化良好的脂肪肉瘤进展到去分化的脂肪肉瘤的机制。为了进一步确定c-Jun在脂肪肉瘤进展中的作用，我们对一系列脂肪肉瘤（n = 81）进行了c-Jun及其活化激酶ASK 1的免疫组织化学。We.将结果与荧光原位杂交相关联以检测c-Jun扩增。我们还从去分化的脂肪肉瘤中获得了新的细胞系，并进行了c-Jun扩增。c-Jun蛋白在大多数去分化脂肪肉瘤（91%）及其高分化成分（59%）中表达，但仅在少数纯高分化脂肪肉瘤（27%）中表达。当c-Jun在去分化的脂肪肉瘤中扩增时，其在环状和巨大标记染色体上散布有扩增的MDM 2。MDM 2扩增是脂肪肉瘤发展中最早的事件之一，这些结果表明，c-Jun在肿瘤演变的相似时间扩增。此外，在c-Jun扩增的脂肪肉瘤细胞中，针对c-Jun的shRNA在体外减少细胞数量，并在体内抑制肿瘤形成，而对脂肪肉瘤细胞的分化状态没有可观察到的影响。因此，c-Jun扩增在脂肪肉瘤中是致癌的，但并不总是足以抑制脂肪细胞分化。版权所有（C）2009大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We. correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.