DOWN-REGULATION OF C-MYC AND MAX GENES IS ASSOCIATED TO INHIBITION OFPROTEIN PHOSPHATASE 2A IN K562 HUMAN LEUKEMIA-CELLS

Treatment of the human myeloid leukemia K562 cells with the protein ph osphatase inhibitors okadaic acid or calyculin A resulted in down-regu lation of both c-myc and max genes at the mRNA and protein levels. The extent of the down-regulation was similar for both genes and was depe ndent on the dose and on the treatment time. Interestingly, c-myc and max down-regulation was concomitant with apoptosis induced by okadaic acid and calyculin A in K562 cells. The expression of c-myc and max re turned to control levels after the removal of okadaic acid from the me dia, although apoptosis was irreversible. These effects were observed at okadaic acid concentrations (15 nM) that inhibited the activity of protein phosphatase type 2A but not of phosphatase type 1. We conclude that the inhibition of protein phosphatase 2A is associated to decrea sed levels of c-Myc/Max heterodimers in K562 cells. (C) 1995 Academic Press, Inc.