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为阐明新基因JWA的结构特征、表达调节规律和生物学功能,通过基因重组和测序,确定了大鼠JWA同源基因和人JWA基因 621 hp的启动子序列;用 RT-PCR法,分析了培养细胞株和原代白血病细胞经药物处理后JWA mRNA的表达情况,发现TPA处理后JWA mRNA水平在肿瘤细胞株与非肿瘤细胞株中是反向变化;用维甲酸治疗前的M3型白血病人骨髓白细胞,其JWA基因对多种诱导分化剂处理不敏感;而用维甲酸治疗 10 d后再用诱导分化剂处理,则 JWA基因的转录水平均被下调,提示 M3型白血病细胞在ATRA作用下的分化可能是启动JWA信号转导通路的前提,而JWA基因的表达下调是否为白血病细胞进一步分化及4HPR,As2O3和TPA等诱导细胞凋亡所必需,值得进一步探讨.JWA基因在不同种属中保持较为稳定的序列特征,说明该基因在生物进化中可能较保守并可能具有相近的生物学功能.
In order to elucidate the structural characteristics, regulation of regulation and biological functions of JWA, the promoter sequence of rat JWA homologue and human JWA gene 621 hp was determined by gene recombination and sequencing. Cultured cell lines and primary leukemia cells after treatment of JWA mRNA expression and found that the level of JWA mRNA after TPA treatment in tumor cell lines and non-tumor cell lines is the reverse change; with retinoic acid before treatment of type M3 leukemia Myeloid leukemia cells, JWA gene is not sensitive to a variety of induced differentiation agent treatment; and retinoic acid treatment for 10 days and then induced differentiation agent, the JWA gene transcription levels were down, suggesting that M3 leukemia cells under the action of ATRA Differentiation may be the prerequisite for initiating JWA signaling pathway. However, whether JWA gene expression is down-regulated in leukemic cells and induced by 4HPR, As2O3 and TPA is worth further study. JWA gene in different species to maintain a more stable sequence characteristics, indicating that the gene may be more conservative in biological evolution and may have similar biological functions.