Level of interleukin-8 expression by metastatic human melanoma cells directly correlates with constitutive NF-κB activity

被引:45
|
作者
Huang, SY [1 ]
DeGuzman, A [1 ]
Bucana, CD [1 ]
Fidler, IJ [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol 173, Houston, TX 77030 USA
关键词
melanoma; IL-8; NF-kappa B; angiogenesis; metastasis;
D O I
10.1080/13684730050515868
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The purpose of this study was to determine whether constitutive NF-kappa B activity regulates the expression level of interleukin-8 (IL-8) in metastatic human melanoma cells. Cultures of metastatic human A375 melanoma cells expressed higher levels of IL-8 mRNA and protein than nonmetastatic A375 human melanoma cells. No discernible differences in IL-8 half-life were found between metastatic and nonmetastatic cells, hut cells that overexpressed IL-8 had a higher transcription rate and increased IL-8 promoter activity. Analysis of the IL-8 promoter using deletion mutants revealed that the region within -133 was essential for constitutive IL-8 promoter activity and that mutation of NF-kappa B binding sites eliminated the constitutive IL-8 promoter activity. The activation of constitutive IL-8 transcription directly correlated with the level of constitutive NF-kappa B activity. Transfection of melanoma cells with a dominant-negative mutant I kappa B alpha expression vector (pLXSN-I kappa B alpha M) significantly decreased the level of constitutive NF-kappa B activity and expression of IL-8, demonstrating that constitutive NF-kappa B/relA activities contribute to overexpression of IL-8 in highly metastatic human melanoma cells.
引用
收藏
页码:9 / 17
页数:9
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