By J. Hofmann, M. Sommer, E. Jarosch, U. Lenk, L. Hein
During this quantity of stories of body structure we current 3 articles on modulation of PKC in antitumor therapy, compartment-specific features of the ubiquitin-proteasome pathway and transgenic versions of alpha2-adrenergic receptor subtype functionality.
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However, a 24-hour exposure to TPA followed by gemcitabine resulted in synergistic cytotoxicity. , 1998). Overexpression of PKC~ in U937 histiocytic Iymphoma cells increased expression of PKCo~and [3 isoforms. In response to TPA, parental U937 ceils displayed growth arrest and differentiated into a monocyte/macrophage-like ceil line, while PKC~ overexpressing ceils underwent death. , 1995). , 1994). , 1993). , 1996). , 1989). A23187 was found to induce apoptosis in immature mouse thymocytes. The addition of TPA at low concentration inhibited the DNA fragmentation induced by A23187 and was accompanied by an increase in DNA synthesis.
1992). TPA increased the phosphorylation of PGP 6-fold and selectively decreased the accumulation of vinblastine in MCF-7/ADR cells. The actions of TPA did not require new synthesis of PGP, and had similar effects in MCF-7/BC-19 cells transfected with a eDNA for PGP. Transfection of MDR1 expressing MCP-7 cells with an expression vector containing PKCct antisense reduced PKCa levels and decreased total PKC activity by 75%. This was accompanied by reduced phosphorytation of PGP, a 2-fold increase in drug retention, and a 3-fold increase in adriamycin cytotoxicity (Ahmad and Glazer, 1993).
1996). , 1990). , 1991). 7-fold, respectively, in the membrane of MOLT-3 and resistant cells, resulted in small increases (rather than decreases) in resistance to adriamycin, whereas for vincristine no consistent trend was observed. Identical results were also obtained with PdBu. These results indicated that PKC activity can be decreased or increased in multidrug resistant cells. Both staurosporine inhibition and phorbol ester activation failed to produce changes in drug resistance that would be considered consistent with the resulting degree of PKC activity.