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

Publikace: BLOOD CELLS MOLECULES AND DISEASES 26, 395-406 Autoři: Vodicka, P., Sevcikova, S., Smardova, J., Soucek, K., Smarda, J. Rok: 2000


Retinoids are important agents which regulate differentiation and proliferation processes in various cell types, including cancer cells. Growth arrest and induction of terminal differentiation demonstrate the tumor-suppressive effects of retinoids on leukemic cells. We studied differentiation, proliferation, and death processes in the cell line of v-myb-transformed monoblasts BM2 and their retinoic acid receptor (RAR) alpha- and retinoid X receptor (RXR) ct-expressing derivatives after exposure to four different retinoids: all-trans retinoic acid, 9-cis retinoic acid, TTNPB, and LG1000153. The effects of retinoids on the phenotype of BM2, BM2RAR, and BM2RXR cells were correlated with the transcription activation function of the v-Myb oncoprotein of avian myeloblastosis virus. We found that the efficiency of terminal differentiation of BM2RAR and BM2RXR cells induced by retinoids is indirectly proportional to the v-Myb transcription activation activity. In contrast, 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 efficient in cell cycle arrest and rather decreases cellular viability. This process can occur in the presence of active v-Myb protein. These results suggest that ligand-activated RAR alpha protein is primarily engaged in control of proliferation and differentiation of v-myb-transformed monoblasts, while activated RXR alpha protein controls their differentiation and death, (C) 2000 Academic Press.