Suppression by protein kinase C inhibitors of tumor promoter enhancement of Epstein-Barr virus-induced growth transformation
Kinoshita, T.; Takahashi, I.; Kobayashi, E.; Tamaoki, T.; Irie, K.; Koshimizu, K.; Osato, T.
Anticancer Research 10(4): 1051-1054
1990
ISSN/ISBN: 0250-7005 PMID: 1696445 Document Number: 355689
The tumor promoter teleocidin activities latent Epstein-Barr virus (EBV) genomes and enhances EBV-induced growth transformation of human B cells, with an activity comparable to that of 12-0-tetradecanoyl-phorbol-13-acetate (TPA). It has been suggeted that the TPA induction of EBV genomes is mediated by protein kinase C (PKC), an enzyme closely linked to signal transduction. We examined newly isolated, highly selective PKC inhibitors, UCN-01 (7-hyroxyl-staurosporine) and calphostin C, for the possible suppression of teleocidin enhancement of cord blood B lymphocyte growth transformation by EBV. 0.2 nM teleocidin B4 enhanced EBV-induced 3H-thymidine uptake 6 times, outgrowth in limiting dilution culture 5 times, and colony formation in semisolid agar 3 times. All these events were suppressed by exposure to 10-100 nM UCN-01 or to calphostin C. Our findings suggest that the tumor promoter enhancement of EBV growth transformation is probably mediated by PKC.