MAPK‐dependent expression of p21WAF and p27kip1 in PMA‐induced differentiation of HL60 cells

Abstract
Treatment of HL60 cells with phorbol 12‐myristate 13‐acetate (PMA) results in growth arrest and differentiation towards the macrophage lineage. PMA‐induced changes are easily monitored by morphological changes while cells in suspension start adhering onto substrate. PMA induces rapid activation of the extracellular signal‐regulated kinases (ERKs). Activation of the ERK pathway is essential to PMA‐induced differentiation of HL60 cells. PMA also induces the expression of the cyclin‐dependent kinase inhibitors p21WAF and p27kip1, which is modulated by the use of an inhibitor of the ERK cascade. This implies that a link exists between ERK activation and p21WAF and p27kip1 induction in the process of terminal differentiation.