The effects of RAR alpha and RXR alpha proteins on growth, viability, and differentiation of v-MYB-transformed monoblasts

Retinoids are important agents which regulate differentiation and prolifera tion processes in various cell types, including cancer cells. Growth arrest and induction of terminal differentiation demonstrate the tumor-suppressiv e effects of retinoids on leukemic cells. We studied differentiation, proli feration, and death processes in the cell line of v-myb-transformed monobla sts BM2 and their retinoic acid receptor (RAR) alpha- and retinoid X recept or (RXR) ct-expressing derivatives after exposure to four different retinoi ds: all-trans retinoic acid, 9-cis retinoic acid, TTNPB, and LG1000153. The effects of retinoids on the phenotype of BM2, BM2RAR, and BM2RXR cells wer e correlated with the transcription activation function of the v-Myb oncopr otein of avian myeloblastosis virus. We found that the efficiency of termin al differentiation of BM2RAR and BM2RXR cells induced by retinoids is indir ectly proportional to the v-Myb transcription activation activity. In contr ast, the effects of liganded retinoid receptors on growth of BM2 cells are more complex. Activated RAR protein induces growth inhibition of BM2 cells by suppression of v-Myb function. However, liganded RXR protein is less eff icient in cell cycle arrest and rather decreases cellular viability. This p rocess can occur in the presence of active v-Myb protein. These results sug gest that ligand-activated RAR alpha protein is primarily engaged in contro l of proliferation and differentiation of v-myb-transformed monoblasts, whi le activated RXR alpha protein controls their differentiation and death, (C ) 2000 Academic Press.