TRANSCRIPTION FACTOR EGR-1 IS INVOLVED IN PHORBOL 12-MYRISTATE 13-ACETATE-INDUCED MEGAKARYOCYTIC DIFFERENTIATION OF K562 CELLS

Transcription factors play important roles in regulating cell growth and differentiation. egr-1, a transcription factor of the zinc finger family, is rapidly activated in many types of cells after mitogen treatment. In this report, we demonstrate that egr-1 mRNA expression, detected by Northern blotting, is activated within 30 min of treatment of the erythroleukemia cell line K562 with phorbol 12-myristate 13-acetate (PMA), and the increased egr-1 mRNA level is associated with an elevated egr-1 antigen expression detected by Western blotting and with its DNA binding activity shown by the gel mobility shift assay In addition, PMA-mediated activation of egr-1 mRNA expression involves no new protein synthesis and is followed by sequential down-regulation of the mRNA level of GATA-1 and glycophorin A. On the other hand, CD41a surface antigen expression is dramatically up-regulated. Furthermore, enforced expression of egr-1, through transfection of K562 cells with the egr-1 expression plasmid construct, results in expression of the egr-1 transcript that accompanies a significant accumulation on the cell surface of CD41a but not CD14 nor glycophorin A. These observations suggest that egr-1 is involved in regulating PMA-induced megakaryocytic differentiation of K562 cell line.