The protein kinase C ?-specific inhibitor LY379196 blocks TPA-induced monocytic differentiation of HL60 cells the protein kinase C ?-specific inhibitor LY379196 blocks TPA-induced monocytic differentiation of HL60 cells

Abstract

The ability of the promyelocytic leukemia HL60 cell line to differentiate in response to various stimuli has provided a widely used model of differentiation. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), acting via its cellular receptor protein kinase C(PKC), induces these cells to acquire a monocytic phenotype. We set out to identify the specific isoform of the multigene PKC family that is involved in this differentiation event. To do so, we utilized a highly specific PKCβ inhibitor, LY379196. We found that LY379196 could prevent the growth arrest, cellular adherence, and changes in several marker proteins that occur after the addition of TPA to HL60 cells and that these effects were not simply due to nonspecific cytotoxicity. Thus, the present studies provide strong evidence that the β isoform of PKC plays a critical role in TPA-induced HL60 monocytic differentiation. Mol. Carcinog. 27:166–176, 2000. © 2000 Wiley-Liss, Inc.