Expression Of RON In Hodgkin’s Lymphoma And Its Impact On Cell Proliferation

Objective:The aim of this study was to investigate the expression of RON in Hodgkin lymphoma; To explore the effects of changing RON expression on proliferation and apoptosis in L428lymphoblastoid cells.Methods:Expression of RON was detected by immunohistochemistry in high density of tissue chip of HL; In situ hybridization technique was used to detect the expression of EBER for EBV status on tissue microarray sections; To determine the effects of EBV stimulation on RON expression in L428cells by intimate contact method; The effect of MSP and Zt/f2(2F2) treatment on proliferation of L428cells was detected by MTT assay, in the mean time the apoptosis were tested through the Annexin V/PI double staining with flow cytometry; Western blotting was used to test phosphorylation of RON and activation of related signaling molecules; Statistical significance was defined as p<0.05, SPSS13.0statistic analysis software was used for analysis. Results:(1)RON expression was obtained in21(47.86%) cases of HL, including2out of the11cases of nodular lymphocyte-predominant,19of the33cases of clinical HL. differences were found between two subtypes (p=0.023); EBER expression was obtained in26cases (59.09%). There was significantly positive correlation between EBV status and abnormal expression of RON in HL tissue (rs=0.324, p<0.05).(2) RON expression significantly increased in EBV-infected L428cells, and is closely related with the LMP1expression.(3) MSP-induced RON activation enhances the proliferation of L428cells, leading to the activation of downstream signaling proteins. On the contrary, Zt/f2decreased expression of RON, and induced apoptosis of L428cells.Conclusion:EBV-induced RON activation may be involved in the pathogenesis of HL.