Vascular endothelial growth factor stimulates protein kinase CßII expression in chronic lymphocytic leukemia cells

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BlankBlood, 3 June 2010, Vol. 115, No. 22, pp. 4447-4454

Vascular endothelial growth factor stimulates protein kinase CßII expression in

chronic lymphocytic leukemia cells

Simon T. Abrams1,*, R. B. Brown1,*, Mirko Zuzel1, and ph R.

Slupsky1

1 Division of Haematology, School of Cancer Studies, University of Liverpool,

Liverpool, United Kingdom

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 CßII (PKCßII), 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 PKCßII expression in CLL cells.

Here we show that the activation of PKCßII in CLL cells stimulated with vascular

endothelial growth factor (VEGF) can drive expression of the gene for PKCß,

PRKCB1. We found that this effect of VEGF on PRKCB1 transcription is paralleled

by high expression of PKCßII 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 PKCßII, an enzyme with a

specific pathophysiologic role in CLL.