Regulation of NFκB/P65 by MDM2 in pediatric acute lymphoblastic leukemia

Abstract

MDM2 was transfected to acute lymphoblastic leukemia (ALL) line EU-4 cell which lacks P53 expression and expresses very low levels of MDM2. The results showed that MDM2 upregulated P65 expression in mRNA level and protein level. The effect of adriamycin (ADM) on MDM2-transfected EU-4 cell was detected by MTT assay. It was found that MDM2 transfection could increase drug resistance of EU-4 cells to ADM as compared with parent cells. Since the expression of E-selectin is P65 dependent, E-selectin promoter-CAT construct and P65 and MDM2 expression plasmids were co-transfected to EU-4 cells, revealing that MDM2 increased P65-mediated transactivation of E-selectin promoter. In the absence of P65, MDM2 had no effect on the transactivation of E-selectin. Moreover, MDM2 antisense couldn’t change the transactivation of E-selectin. It was concluded that MDM2 could up-regulate transcriptionally P65 expression; MDM2 increased drug resistance of leukemia cells to ADM; MDM2 elevated NF-kappaB activity in a P53-independent manner.

Keywords

acute lymphoblastic leukemia / MDM2 / NF-κB

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