Expression of the Elm1 gene, a novel gene of the CCN (connective tissue growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family, suppresses In vivo tumor growth and metastasis of K-1735 murine melanoma cells.

Expression of the Elm1 gene, a novel gene of the CCN (connective tissue growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family, suppresses In vivo tumor growth and metastasis of K-1735 murine melanoma cells.
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DOI:
10.1084/jem.187.3.289
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发表时间:
1998-02-02
影响因子:
15.3
通讯作者:
Yokota, J
Yokota, J
中科院分区:
医学1区
文献类型:
--
作者:
Hashimoto, Y;Shindo-Okada, N;Tani, M;Nagamachi, Y;Takeuchi, K;Shiroishi, T;Toma, H;Yokota, J

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我们之前分离了一个新基因Elm1(在低转移细胞中表达)的部分cDNA片段,该基因在低转移而不是高转移的K-1735小鼠黑色素瘤细胞中表达。我们测定了Elm1的全长cDNA结构,并研究了Elm1表达对K-1735细胞生长和转移潜能的影响。Elm1基因编码367个氨基酸的预测蛋白,与CCN(结缔组织生长因子[CTGF], Cyr61/Cef10,神经母细胞瘤过表达基因[Nov])家族蛋白具有约40%的氨基酸同源性,该家族蛋白由分泌的富含半胱氨酸的蛋白组成,具有生长调节功能。Elm1也是一种富含半胱氨酸的蛋白,在CCN家族蛋白中包含一个信号肽和四个保守结构域。Elm1高度保守,在不同器官中普遍表达,并定位于小鼠第15号染色体。用Elm1表达载体转染不表达Elm1的高转移性K-1735 M-2细胞,建立了几个表达Elm1的稳定克隆。高表达Elm1的细胞的体内生长速度明显慢于低表达Elm1的细胞。转染的转移潜能与Elm1表达水平成比例降低。因此,Elm1是CCN家族的一个新基因,可以抑制K-1735小鼠黑色素瘤细胞的体内生长和转移潜力。
We previously isolated a partial cDNA fragment of a novel gene, Elm1 (expressed in low-metastatic cells), that is expressed in low-metastatic but not in high-metastatic K-1735 mouse melanoma cells. Here we determined the full-length cDNA structure of Elm1 and investigated the effect of Elm1 expression on growth and metastatic potential of K-1735 cells. The Elm1 gene encodes a predicted protein of 367 amino acids showing ∼40% amino acid identity with the CCN (connective tissue growth factor [CTGF], Cyr61/Cef10, neuroblastoma overexpressed gene [Nov]) family proteins, which consist of secreted cysteine-rich proteins with growth regulatory functions. Elm1 is also a cysteine-rich protein and contains a signal peptide and four domains conserved in the CCN family proteins. Elm1 was highly conserved, expressed ubiquitously in diverse organs, and mapped to mouse chromosome 15. High-metastatic K-1735 M-2 cells, which did not express Elm1, were transfected with an Elm1 expression vector, and several stable clones with Elm1 expression were established. The in vivo growth rates of cells expressing a high level of Elm1 were remarkably slower than those of cells expressing a low level of Elm1. Metastatic potential of transfectants was reduced in proportion to the level of Elm1 expression. Thus, Elm1 is a novel gene of CCN family that can suppress the in vivo growth and metastatic potential of K-1735 mouse melanoma cells.
DOI: 10.1126/science.3541204
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期刊: SCIENCE
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