Retinoid X receptor α is highly phosphorylated in retinoic acid-resistant HL-60R cells and the combination of 9-cis retinoic acid plus MEK inhibitor induces apoptosis in the cells

We examined the effects of 9-cis retinoic acid (RA) on the expression levels of retinoid X receptor α (RXRα) and its phosphorylated form (p-RXRα) in HL-60 and HL-60R cells. 9-cis RA reduced both RXRα and p-RXRα in HL-60 cells, but did neither in HL-60R cells. However, when the HL-60R cells were treated with the combination of 9-cis RA plus PD98059, MEK inhibitor, the p-RXRα and RXRα proteins all markedly decreased. Moreover, the combination of those agents induced apoptosis in HL-60R cells. Phosphorylation of RXRα might be associated with RA-resistance in HL-60R cells.