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.
