肝癌缺失基因-1在多发性骨髓瘤中的作用及甲基化研究-内科血液病学专业论文.docxVIP

山西医 山西医科大学博士学位论文 IV IV GFP 融合蛋白形成，转染细胞效率达到 70%以上。 结论：采用体外重组技术，成功地将人 DLC-1 cDNA 插入了荧光蛋白表达载体 pEGFP-N1 中，为后期其在细胞中的定位、功能及调节通路研究奠定了实验基础。 关键词 多发性骨髓瘤；肝癌缺失基因-1；肿瘤抑癌基因；甲基化；地西他滨(达珂)；U266； Transwell。 PAGE PAGE VI Abstract Multiple myeloma is a kind of incurable malignancy of end stage B-lineage cells, and characterized by an accumulation of neoplastic plasmia cells in the bone marrow and invasion into other organs. Clinical manifestations of MM because of the accumulation of plasma cells in the bone marrow and excessive levels of monoclonal immunoglobulin can result in osteolytic lesions, anema, myelosuppression and renal dysfunction. Cytogenetic, immunization and cytokine have been linked to the development fo MM. It is becoming clear that in addition to genetic aberrations, epigenetic processes play a major role in carcinogenesis. DLC-1 gene is frequently deleted in hepatocellular carcinoma. The absence or down-regulation of DLC-1 was detected in many cancer or tumor cell lines, such as, DLC-1 promoter hypermethylation has been linked to the transcription silencing of DLC and is the major epigenetic mechanism associated with loss of tumor suppressor gene function. Tannscriptional silencing promoter hypermethylation of DLC-1has been detected in over 80% of patients with acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. Similar consequence was also observed in MM cells lines. However, the correlation between expression and methylation of DLC-1 and clinical characteristics in MM patients has not been identified. To identify whether DLC-1 was associtated with the pathogenesis of multiple myeloma, we examined the expression and hypermethylation of DLC-1 in MM patients and MM cell line U266, observed the effect the changers of biological behaviour of U266 after treated with Decitabine at varying concentrations. In addition, to investigate the function of isform 1 of DLC-1, the eukaryotic expression vector of GFP-DLC-1 was constructed. Chapter one The study on ex