Retinoid X receptor alpha 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 alpha (RXR alpha) and its phosphorylated form (p-RXR alpha) in HL-60 and HL-60R cells. 9-cis RA reduced both RXR alpha and p-RXR alpha 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-RXR alpha and RXR alpha proteins all markedly decreased. Moreover, the combination of those agents induced apoptosis in HL-60R cells. Phosphorylation of RXR alpha might be associated with RA-resistance in HL-60R cells.