Evidence that activation of MEK1,2/erkl,2 signal transduction pathway is necessary for calcitriol-induced differentiation of HL-60 cells

Calcitriol (1,25-dihydroxyvitamin D-3) induces differentiation and inhibits proliferation of human promyelocytic leukemia cells. The mechanisms involv ed in the regulation of these processes are not clearly understood. Previou s studies have shown that calcitriol mediates cell differentiation not only by interaction with nuclear vitamin D receptor, but also by numerous rapid , membrane - mediated effects. Since in the light of past studies, involvem ent of raf/MEK1,2/erk1,2 signal transduction pathway in calcitriol-induced cell differentiation was questionable, another attempt was undertaken in th is study in order to investigate the problem. PD 98059, the specific inhibi tor of MEK1 and MEK2 was found to inhibit calcitriol-induced monocytic diff erentiation of HL-60 cells. This finding proves that activation of the raf/ MEK1,2/erk1,2 signal transduction pathway is essential for monocytic differ entiation of human leukemia cells. The results reported in this paper sugge st that inhibition of protein kinase C, which upstream regulates activation of erk1 and erk2, may be bypassed during the process of calcitriol-induced leukemia cell differentiation.