SURVIVAL BY MAC-1-MEDIATED ADHERENCE AND ANOIKIS IN PHORBOL ESTER-TREATED HL-60 CELLS

During the exposure of human myelocytic leukemia HL-60 cells to phorbo l diester, nonadherent cells die by apoptosis, but adherent cells surv ive rand growth-arrest at G(1) phase of the cell cycle. Here we have s hown that the adherent cells rapidly died by apoptosis after forced de tachment (anoikis), indicating that phorbol diester induced apoptosis by default. Dimethylsphingosine induced apoptosis in the adherent cell s, and sphingosine-1-phosphate rescued the detached cells from apoptos is, Sphingosine kinase activity in adherent cells was higher than that in nonadherent cells and was decreased by forced detachment. It is li kely that the phorbol diester-induced apoptosis and the adhesion-media ted survival are modulated by sphingosine and sphinposine-1-phosphate, respectively. The adherent cells were reverted and reproliferated whe n allowed to spontaneously detach from plastic surfaces by removal of phorbol tliester, This result suggests that after removal of phorbol d iester, the commitment signal of apoptosis by default is lost faster t han the survival signal by adherence.