Ras and Rac1, frequently mutated in melanomas, are activated by superoxide anion, modulate Dnmt1 level and are causally related to melanocyte malignant transformation.

摘要: A melanocyte malignant transformation model was developed in our laboratory, which different melanoma cell lines were obtained after submitting the non-tumorigenic lineage melan-a to sequential cycles of anchorage impediment. Our group has already showed that increased superoxide level leads global DNA hypermemethylation as well Dnmt1 expression few hours blockade. Here, we Ras/Rac1/ERK signaling pathway is activated melanocytes submitted impediment, regulating levels, methylation, and expression. Interestingly, Ras Rac1 activation not related codon mutations, but instead regulated by superoxide. Moreover, drastically compromised when blockage presence a scavenger. This aberrant associated with sustained stressful condition, might be similar conditions such UV radiation inflammation, seems an early step contribute epigenetic reprogramming development.