INCREASE OF NUCLEAR PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE AND PHOSPHOLIPASE-C BETA(1) IS NOT ASSOCIATED TO VARIATIONS OF PROTEIN-KINASE-C IN MULTIDRUG-RESISTANT SAOS-2 CELLS

The multidrug resistance (MDR) phenotype that is mediated by an overex pression of P-glycoprotein, has been suggested to be related also to a n increased activity of protein kinase C (PKC) and to changes in phosp holipid pattern. By electron microscope quantitative immunocytochemist ry, we investigated whether PKC and other elements of the polyphosphoi nositide signal transduction system are affected in an MDR variant of the human osteosarcoma cell line Saos-2. These cells, which are charac terized by an increased expression of P-glycoprotein not only at the p lasma membrane but also at the nuclear level, showed increased intranu clear amounts of phosphatidylinositol 4,5-bisphosphate and of phosphol ipase C beta(1), while both the amount and activity of both nuclear an d cellular PKC were not modified with respect to sensitive cells. Thes e results suggest that, in this model, the changes observed in the ele ments of nuclear signal transduction could be related to previously re ported modifications of the MDR phenotype, but that P-glycoprotein pho sphorylation is not dependent from increased PKC activity. (C) 1997 Wi ley-Liss, Inc.