Significance Of Expression And Promoter Methylation Of LITAF Gene In B-cell Lymphoma

LITAF, encoding228amnio acid, was initially identified as the P53-inducible gene. Subsequent studies have fuctionally characterized LITAF as an activator of the secretion of inflammatory cytokines, such as TNF-a, upon lipopolysaccharide (LPS) stimulation, acting as a transcriptional activator of TNF-a. Recently, several lines of evidence have indicated possible roles of pig7abnormality in pathogenesis of some malignancies including thyroid carcinoma, breast cancer and lymphoma. DNA methylation is an important means of regulating transcription of genes, the researches found that hypermethylation of tumor suppressor gene could induce gene silencing and closed related with hematopoietic tumors. In this study, we investigated the promoter methylation status of LITAF gene in B-cell lymphoma and explored the transcription regulation of5-Aza-2’-deoxycytidine (5-Aza-CdR) on LITAF gene.One hundred and five paraffin B-NHL specimens including54cases of diffuse large B cell lymphoma (DLBCL),15of small lymphocytic lymphoma (SLL),8of mucosa-associated lymphoid tissue lymphoma (MALT) and6of follicular lymphoma (FL) were studied. Five reactive hypertrophic lymphoid tissues were collected as a control. Methylation state of CpG island in LITAF gene in the specimens and Raji, Pfeiffer and Daudi cell lines were detected by MSP. LITAF expression in Raji, Pfeiffer and Daudi cell lines with or without5-Aza-CdR treatment were detected by Western blot and immunohistochemistry. The inhibitory ratio of this three cell lines were measured by MTT assay.The frequency of LITAF gene methylation in B-cell lymphoma was89.5%. Among them,4cases showed complete hypermethylation. In control group, however, there was no methylation in CpG island of LITAF gene promoter. The expression of LITAF was recovered or increased and the cell growth was inhibited when the cells exposed to the demethylating reagent. LITAF gene silencing with aberrant CpG methylation is probably one of the critical events to the oncogenesis of B-cell lymphoma as well as important implications for the candidate diagnostic markers and the target of gene therapy.