Identification of the @entity3546 / XXXX / @entity30405 @entity2270 as a novel target of @entity2857 in @entity157 cells.

@entity1 @entity5 @entity2857 @entity3546 @entity30405 @entity1639 @entity58620 @entity4675 @entity2270 @entity157 @entity4334
UNASSIGNED: @entity2857 is a kinase inhibitor used as anticancer drug against various @entity1 @entity5 , including advanced @entity157 ( @entity157 ). @entity3546 and @entity30405 ( @entity58620 ) are overexpressed in @entity157 and other @entity5 . Previous studies have shown that @entity58620 expression modulates the response of @entity157 cells to @entity2857 . However, the underlying mechanism of @entity58620 activity in this context remains unclear. We show here that @entity2857 inhibits both @entity3546 and @entity58620 in a dose-dependent manner. Silencing @entity3546 reduces @entity58620 level and sensitizes @entity157 cells to @entity2857 . In contrast, ectopic expression of @entity3546 induces @entity58620 expression and cell resistance to the drug. @entity2857 inhibits @entity58620 expression at the transcriptional level by inhibiting the @entity3546 pathway. @entity4334 deletion analysis of the @entity58620 gene promoter reveals that a DNA segment lying 1,500-1,600 bp upstream of the @entity58620 transcription start site represents an AP-1-binding site that is critical for @entity3546 modulation of gene transcription in response to @entity2857 . In addition, chemical inhibitors that target @entity4675 abrogate @entity3546 /AP-1 binding to the endogenous @entity58620 gene and reduces @entity58620 transcription and protein expression. Silencing of @entity3546 or @entity1639 induces similar effects on gene regulation and these are reversed by ectopic expression of @entity3546 . Mutations in the @entity58620 promoter at the predicted @entity3546 /AP-1 binding site partly abrogate @entity2857 's effects on @entity58620 transcription. These results indicate that @entity58620 is induced by the oncoprotein @entity3546 and protects @entity157 cells against @entity2857 -induced cell death. The @entity3546 / @entity4675 / @entity58620 @entity2270 may thus represent a novel target for chemotherapy against @entity157 .
