PHORBOL ESTER-INDUCED ALTERATION OF DIFFERENTIATION AND PROLIFERATION IN HUMAN HEMATOPOIETIC TUMOR-CELL LINES - RELATIONSHIP TO THE PRESENCE AND SUBCELLULAR-DISTRIBUTION OF PROTEIN KINASE-C

Abstract

The intracellular translocation of protein kinase C (PKC) from the soluble to the membranous fraction has been shown previously to correlate with biological activity or phorbol esters in several systems. In this paper, we described that PKC translocaiton was a general phenomenon in all PKC containing cell types when five 12-O-tetradecanoylphorbol-13-acetate (TPA) responsive and nonresponsive hematopoietic tumor cell lines were investigated. The nonresponsive cell line U-266 contained undetectable levels of PKC. The dose of TPA required for translocation was similar to the TPA concentration necessary to suppress erythroid differentiation in K-562 cells and to induce macrophage differentiation in U937 cells, but 100-fold higher than that required for suppression of proliferation in K-562 and U-937 cells. By contrast, PKC translocation and TPA induced proliferation inhibition a similar dose dependence in a subline of U-937 (U-937RES) adapted to growth in the presence of 10-9 M TPA. It is suggested that U-937RES is deficient in a TPA dependent but PKC independent signal pathway.