Ly-GDI Construction, Expression And Mechanism In L428 Cells

Hodgkin's Disease(HD) is a kind of malignant lymphoma. Hodgkin and Reed-Sternberg(HRS) cells, the malignant cell population in Classical Hodgkin lymphoma(cHL) asise from germinal center(GC) B cells.HRS cells display resistance to certain apoptotic stimuli,including a lack of sensitivity to Fas-mediated apoptosis.However,the machanisms responsible for their resistance to apoptosis inducers have not been elucidated.Ly-GDI is the lymphoid-specific guanosine diphosphate (GDP) dissociation inhibitor.The full length Ly-GDI cDNA encodes a 27-KD protein which binds to RhoA and inhibits GDP dissociation from RhoA.Because of the widespread expression of LyGDI in hematopoetic cells and B-NHL cell lines, its degradation during apoptosis and its absence in Hodgkin cell lines we reasoned that classical Hodgkin lymphoma might lack expression of LyGDI in situ and the absence of LyGDI might contribute to the apoptotic resistance of HRS.We showed that the Hodgkin cell line L428 and primary Hodgkin cells in vivo lack expression of LyGDI. Furthermore, we investigated the role of LyGDI in Hodgkin cells by expressing full length LyGDI in L428 Hodgkin cells in vitro. Our data suggest, that expression of LyGDI in L428 increase the level of apoptosis and cell death only in a subset of cells, whereas the majority of cells survive LyGDI expression. Expression of LyGDI does not increase chemosensitivity or sensitivity to receptor induced cell death in the Hodgkin cell line L428.