Retinoic acid-induced blr1 expression promotes ERK2 activation and cell differentiation in HL-60 cells

Retinoids are known to induce the differentiation and cell cycle arrest of human myeloid leukemia cells in vitro. Differential display was used to ide ntify putative early regulatory genes that are differentially expressed in HL-60 human promyelocytic leukemia cells treated with retinoic acid. One of the cDNAs cloned encodes sequences identifying Burkitt's lymphoma receptor 1 (BLR1), a recently described chemokine receptor. Northern blot analysis demonstrates that blr1 mRNA expression increases within 9 h of retinoic aci d treatment, well before functional differentiation or G(1)/G(0) growth arr est at 48 h or onset of morphological changes, suggesting a possible regula tory function. The expression of blr1 mRNA is transient, peaking at 72 h wh en cells are differentiated. blr1 mRNA also is induced by other differentia tion-inducing agents, 1 alpha,25-dihydroxyvitamin D-3 and DMSO, Induction o f blr1 mRNA by retinoic acid is not blocked by the protein synthesis inhibi tor cycloheximide, In HL-60 cells stably transfected with blr1 cDNA, ectopi c expression of blr1 causes an increase in ERK2 MAPK activation and promote s retinoic acid-induced G(1)/G(0) growth arrest and cell differentiation. T he early expression of blr1 mRNA during differentiation, its ability to inc rease ERK2 activation, and its enhancement of retinoic acid-induced differe ntiation suggest that blr1 expression may be involved in retinoic acid-indu ced HL-60 differentiation. (C) 2000 Academic Press.