@entity25687 transcriptionally induced by XXXX / @entity16389 is a negative regulator that antagonizes arsenic trioxide-induced @entity5 cell apoptosis.

@entity1 @entity2799 @entity25687 @entity7242 @entity5 @entity4222 @entity16389 @entity470 @entity584 @entity1178 @entity4675 @entity1583 @entity994
Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of @entity2799 . In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other @entity1583 and @entity5 . However, ATO's modest clinical efficacy on some @entity5 , and potential toxic effects on @entity1 have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the @entity4675 -induced complex formation of phosphorylated @entity1178 and @entity25687 ( @entity25687 ) antagonizes ERK-induced cyclin-dependent kinase inhibitor @entity994 ( @entity994 ( @entity994 / @entity994 )) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1-0.2  M), ATO increased cellular proliferation, @entity4222 and invasion, involving @entity25687 expression, however, at high-concentrations (5-20  M), ATO induced cell apoptosis. Using a promoter analysis, @entity25687 was transcriptionally regulated by ATO at the @entity16389 binding site (-1486 to -1479bp) via the @entity7242 / @entity470 / @entity584 pathway. Stable overexpression of @entity25687 promoted advancing the cell cycle into the S phase, and attenuated 20  M ATO-induced apoptosis. Furthermore, blockage of the @entity584 pathway enhanced ATO-induced @entity994 expression and resultant apoptosis in @entity5 cells, but overexpression of @entity584 inhibited @entity994 expression. Therefore, we suggest that @entity25687 is transcriptionally regulated by the @entity7242 / @entity470 / @entity584 pathway, which plays a role as a negative regulator in antagonizing ATO-induced @entity994 expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO.
