Synergistic differentiation of U937 cells by all-trans retinoic acid and 1 alpha, 25-dihydroxyvitamin D3 is associated with the expression of retinoid X receptor alpha.

Among the nuclear hormone receptors, the retinoid X receptors (RXRs) play a central role through their ability to heterodimerize with other members of this family of transcription factors, including retinoic acid (RA) and vitamin D (VD3) receptors. We have previously found that all-trans retinoic acid and 1 alpha, 25-dihydroxyvitamin D3 cooperate to induce monocytic differentiation of U937 human leukemic cells. Here the expression of RXR alpha protein in myelomonocytic cells was studied by immunodetection using polyclonal antibodies. RXR alpha was detected upon exposure of cells to VD3 and higher levels were found in cells treated by combinations of RA and VD3 under conditions where both agents synergized for inducing monocytic properties.