Activation of Phospholipase C γ 2 in Lymphoma Cells.

Abstract

The Nf-κB signaling pathway is important for lymphoma survival and cell proliferation. In recent immunohistological studies, the B-cell receptor (BCR), Src kinases and PLC γ 2 were shown to be highly expressed in primary mediastinal B-cell lymphoma and lymphocyte predominant Hodgkin lymphoma, but not in classical Hodgkin lymphoma. Activation of PLC γ 2 is a crucial step in regulating Nf-κB through protein kinase C (PKC). The PLC-PKC cascade also activates the Ras-Raf-Erk signaling pathway by recruiting GRP3 to the cell membrane. These signaling cascades are well studied in physiological B-cells, but there is little data about the role of PLC γ 2 in lymphomas. Our study compared the PLC γ 2 expression in low-grade gastric MALT lymphoma tissue and chronic gastritis tissue from the same patient by quantitative PCR. In 8 out of 10 cases PLC γ 2 was overexpressed in MALT lymphomas, but not in gastritis. We performed functional studies with the PLC-inhibitor U73122 and PLC γ 2 specific siRNA in two lymphoma cell lines (SSK41, Raji). Proliferation of lymphoma cells was significantly reduced by inhibition of PLC γ 2 on protein level and by knocking down PLC γ 2 mRNA by transfection with a specific siRNA. Our results indicate that proliferation and survival of lymphoma cells depend, at least in part, on the activated PLC-PKC signaling cascade and that it is possible to reduce lymphoma survival by the “small molecule inhibitor” U73122. PLC γ 2 could be a new target for lymphoma treatment.