Vascular endothelial growth factor stimulates protein kinase CbetaII expression in chronic lymphocytic leukemia cells.
Chronic lymphocytic leukemia (CLL) is a malignant disease of mature B lymphocytes. We have previously shown that a characteristic feature of CLL cells are high levels of expression and activity of protein kinase CbetaII (PKCbetaII), and that this might influence disease progression by modulating signaling in response to B-cell receptor engagement. The aim of the present work was to investigate the factors involved in stimulating PKCbetaII expression in CLL cells. Here we show that the activation of PKCbetaII in CLL cells stimulated with vascular endothelial growth factor (VEGF) can drive expression of the gene for PKCbeta, PRKCB1. We found that this effect of VEGF on PRKCB1 transcription is paralleled by high expression of PKCbetaII protein and therefore probably contributes to the malignant phenotype of CLL cells. Taken together, the data presented in this study demonstrate that VEGF, in addition to its role in providing prosurvival signals, also plays a role in overexpression of PKCbetaII, an enzyme with a specific pathophysiologic role in CLL.
Abrams
Simon T
ST
Division of Haematology, School of Cancer Studies, University of Liverpool, Liverpool, United Kingdom.
Brown
Benjamin R B
BR
Zuzel
Mirko
M
Slupsky
Joseph R
JR
D000077329:Agammaglobulinaemia Tyrosine Kinase; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism*; D008698:Mesylates / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
C434605:5,21 - 12,17-dimetheneo-18H-dibenzo(i,o)pyrrolo(3,4-1)(1,8)diazacyclohexandecine-18,10(19H)dione,8((dimethylamino)methyl)-6,7,8,9,10,11-hexahydro,monomethanesulfonate; D017931:DNA Primers; D008698:Mesylates; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C579054:PRKCB protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta