期刊
PIGMENT CELL RESEARCH
卷 14, 期 6, 页码 456-465出版社
BLACKWELL MUNKSGAARD
DOI: 10.1034/j.1600-0749.2001.140606.x
关键词
melanocyte; melanoma; NF kappa B; antisense; TNF; UVB
资金
- NCI NIH HHS [CA62203] Funding Source: Medline
Metastatic melanomas are typically resistant to radiation and chemotherapy. The underlying basis for this phenomenon may result in part from defects in apoptotic pathways. Nuclear factor kappa B (NF kappaB) has been shown to control apoptosis in many cell types and normally functions as an immediate stress response mechanism that is rigorously controlled by multiple inhibitory complexes. We have previously shown that NF kappaB binding is elevated in metastatic melanoma cells relative to normal melanocytes. In the current study, Western blot analysis showed that, compared with normal melanocytes, melanoma cell lines have higher nuclear levels of the NF kappaB subunits p50 (7-fold) and RelA (5-10-fold). In response to tumor necrosis factor-alpha (TNF alpha), both melanocytes and melanoma cells showed increased nuclear p50 and RelA levels, but levels in melanoma cells remained higher than in melanocytes. We also found that melanoma cells expressed higher cytoplasmic levels of RelA, p105/p50 and the inhibitory protein, inhibitor of kappa B alpha (I kappaB alpha) than melanocytes. To directly test whether RelA expression has an impact on melanoma cell survival, we used antisense RelA phosphorothioate oligonucleotides and found that melanoma cell viability was significantly decreased compared with untreated or control cultures. The constitutive activation of NF kappaB in metastatic melanoma cell cultures may, therefore, support an inappropriate cell survival pathway that can be therapeutically manipulated.
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