title: cAMP differentially regulates gamma-globin gene expression in erythroleukemic cells and primary erythroblasts through c-Myb expression.
abstract: Our previous studies demonstrated roles of cyclic nucleotides in gamma-globin gene expression. We recently found that, upon activation of the cAMP pathway, expression of the gamma-globin gene is inhibited in K562 cells but induced in adult erythroblasts. Here we show that c-Myb, a proto-oncogene product that plays a role in cell growth and differentiation, is involved in the cAMP-mediated differential regulation of gamma-globin gene expression in K562 cells and primary erythroblasts. Our studies found that c-Myb is expressed at a high level in K562 cells compared to primary erythroblasts, and that c-Myb expression is further increased following the treatment with forskolin, an adenylate cyclase activator. The induction of gamma-globin gene expression was also inhibited in K562 cells by raising the levels of c-Myb expression. Importantly, forskolin-induced erythroid differentiation in K562 cells, as determined by the expression of glycophorins and CD71, suggesting that high-level expression of c-Myb may not be sufficient to inhibit the differentiation of erythroid cells. In contrast, c-Myb was not expressed in adult erythroblasts treated with forskolin and primary erythroblasts may lack the c-Myb-mediated inhibitory mechanism for gamma-globin gene expression. Together, these results show that the cAMP pathway blocks gamma-globin gene expression in K562 cells by increasing c-Myb expression and c-Myb plays a role in defining the mode of response of the gamma-globin gene to fetal hemoglobin inducers in erythroid cells.
authors.affiliation: Institute of Molecular Medicine and Genetics, Department of Medicine, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kuroyanagi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Muta
authors.forename: Buem-Seek
authors.initials: BS
authors.lastname: Park
authors.forename: Paolo
authors.initials: P
authors.lastname: Moi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ausenda
authors.forename: Maria D
authors.initials: MD
authors.lastname: Cappellini
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikuta
mesh_terms: D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004900:Erythroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb; D005914:Globins; D000242:Cyclic AMP