Differential expression and mutation of NME genes in autologous cultured human melanoma cells with different metastatic potentials.
Differential expression and mutation of NME genes in autologous cultured human melanoma cells with different metastatic potentials.
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不同转移潜能的自体培养人黑色素瘤细胞中NME基因的差异表达和突变。
DOI：
10.1006/bbrc.1995.1852
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发表时间：
1995
影响因子：
3.1
通讯作者：
Backer,JM
中科院分区：
文献类型：
--
作者：
Hamby,CV;Mendola,CE;Potla,L;Stafford,G;Backer,JM
假定的转移抑制基因，NME 1（nm 23 -1）和NME 2（nm 23 -2），在我们开发的模型系统中进行了检查，以近似原发性皮肤肿瘤黑色素瘤的传播。我们利用两个自体的人黑色素瘤细胞系，IV Cl 1和IV Cl 3，这表现出定性不同的转移表型皮下接种到裸鼠。高转移性IV Cl 1细胞表达的由NME基因编码的蛋白质水平比非转移性IV Cl 3细胞低约5倍。在裸鼠中由两种细胞系诱导的肿瘤中观察到NME蛋白水平的类似差异。这两种细胞系之间的NME mRNA水平没有差异，表明这些蛋白质的表达在转录后水平受到调控。我们发现转移性IV Cl 1细胞的NME 2基因中存在ser 122-pro突变。在人神经母细胞瘤中发现了NME 1中类似的ser 120-gly突变，表明该区域的突变可能是与肿瘤进展相关的普遍现象。这些突变可能具有功能性后果，因为它们消除了潜在的磷酸化位点，并可能影响成熟蛋白质复合物的三级结构。
The putative metastasis suppressor genes, NME1(nm23-1) and NME2(nm23-2),were examined in a model system we developed to approximate the dissemination of melanoma from a primary skin tumor. We utilized two autologous human melanoma cell lines, IV Cl 1 and IV Cl 3, which displayed qualitatively different metastatic phenotypes following subdermal inoculation into nude mice. Highly metastatic IV Cl 1 cells expressed approximately 5 fold lower levels of proteins encoded by NME genes than non-metastatic IV Cl 3 cells. Similar differences in NME protein levels were observed in tumors induced by the two cell lines in nude mice. There were no differences in NME mRNA levels between these two cell lines, suggesting that expression of these proteins is regulated at a post-transcriptional level. We found a ser122-pro mutation in the NME2 gene of metastatic IV Cl 1 cells. A similar ser120-gly mutation in NME1 has been found in human neuroblastoma, suggesting that mutation in this region may be a general phenomenon related to tumor progression. These mutations may have functional consequences since they eliminate potential phosphorylation sites and may affect the tertiary structure of mature protein complexes.