Redundant functions of B-Myb and c-Myb in differentiating myeloid cells.

作者：Josée Golay, Vania Broccoli, Gian Maria Borleri, Eugenio Erba, Mario Faretta, Luca Basilico, G G Ying, Gina Piccinini, Linda H. Shapiro, Josip Lovrić, Michael Nawrath, Karin Mölling, Alessandro Rambaldi, Martino Introna · 发表于：PubMed · 年份：1997 · 被引用次数：17 · 研究领域：Cancer-related Molecular Pathways、Acute Myeloid Leukemia Research、Retinoids in leukemia and cellular processes

We show in this report that the human myeloid leukemia cell line GFD8 is a useful model to compare the biological function of the structurally related c-Myb and B-Myb proto-oncogenes and to investigate the c-myb domains required for this function. GFD8 cells are dependent for growth on granulocyte-macrophage colony-stimulating factor and differentiate in response to phorbol myristate acetate (PMA). We have stably transfected this cell line with constructs constitutively expressing c-Myb or B-Myb. Deregulated expression of both c-Myb and B-Myb inhibited the differentiation observed in response to PMA and, in particular, the induction of the CD11b and CD11c antigens on the cell surface, and the induction of adherence. Furthermore, c-Myb and B-Myb enhanced expression of CD13 upon PMA treatment. Although deregulated Myb expression did not alter the growth factor dependence of the cells, it led to an increase in G2 relative to G1 arrest in cells induced to differentiate in response to PMA, whereas control vector-transfected cells were blocked mostly in G1. This decrease in G1 block took place despite normal induction of the cyclin-dependent kinase inhibitor protein p21 (CIP1/WAF1). Thus, GFD8 cells stably expressing the human B-Myb protein behaved in a manner indistinguishable from those stably expressing C-Myb for both differentiation and cell cycle parameters. In agreement with these findings and differently from most previous reports, transactivation assays show that B-myb can ...