Two Transcription Factors, E1AF and N‐myc, Correlate with the Invasiveness of Neuroblastoma Cell Lines

Two Transcription Factors, E1AF and N‐myc, Correlate with the Invasiveness of Neuroblastoma Cell Lines
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两种转录因子 E1AF 和 N-myc 与神经母细胞瘤细胞系的侵袭性相关

DOI:
10.1111/j.1349-7006.1997.tb00395.x
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发表时间:
1997
期刊:
Japanese Journal of Cancer Research : Gann
影响因子:
--
通讯作者:
K. Fujinaga
K. Fujinaga
中科院分区:
--
文献类型:
--
作者:
K. Taguchi;Koichi Yoshida;F. Sasaki;K. Fujinaga

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ets转录因子E1 AF可以激活几种基质降解金属蛋白酶(MMP)基因,并参与增强肿瘤细胞侵袭。在这里,我们比较了五种人神经母细胞瘤细胞系(TGW、后藤、SK-N-BE、SK-N-SH和SK-N-AS)的侵袭活性,这些细胞系表现出不同水平的N-myc扩增以及E1 AF表达。还分析了在局部侵袭中起重要作用的细胞外基质降解蛋白酶及其抑制剂蛋白。在具有N-myc扩增的细胞(TGW、后藤和SK-N-BE)中,通过重建的基底膜侵入的活性高,并且这些细胞产生相对大量的E1 AF mRNA,这与侵入活性相关。在几种基质金属蛋白酶(MMP)和MMP的组织抑制剂(TIMP)中,仅在N-myc扩增的细胞中特异性检测到膜结合1型MMP(MT 1-MMP),表明MT 1-MMP在神经母细胞瘤细胞侵袭中的作用。MMP-2(72 kD IV型胶原酶)、TIMP-1和TIMP-2在所有5种细胞系中表达。尿激酶型纤溶酶原激活剂未检出。这些发现表明转录因子E1 AF和N-myc与神经母细胞瘤的恶性表型相关。
The ets transcription factor E1AF can activate several matrix‐degrading metalloproteinase (MMP) genes and is implicated in enhancement of tumor cell invasion. Here we compared the invasive activity of five human neuroblastoma cell lines (TGW, GOTO, SK‐N‐BE, SK‐N‐SH and SK‐N‐AS), which exhibit distinct levels of N‐myc amplification, together with the expression of E1AF. Extracellular matrix‐degrading proteases and their inhibitor proteins, which play an important role in local invasion, were also analyzed. The activity to invade through reconstituted basement membrane was high in cells (TGW, GOTO, and SK‐N‐BE) with N‐myc amplification, and these cells produced relatively large amounts of E1AF mRNA, correlating with the invasive activities. Of several matrix metalloproteinases (MMPs) and a tissue inhibitor of MMPs (TIMP), only membrane‐bound type 1 MMP (MT1‐MMP) was specifically detected in N‐myc‐amplified cells, suggesting a role of MT1‐MMP in neuroblastoma cell invasion. MMP‐2 (72 kD type IV collagenase), TIMP‐1 and TIMP‐2 were expressed in all five cell lines. Urokinase‐type plasminogen activator was undetectable. These findings indicate that the transcription factors E1AF and N‐myc are related to malignant phenotypes of neuroblastoma.
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