摘要目的 探讨低剂量2-甲氧基雌二醇(2ME2)诱导骨髓瘤细胞分化过程中对PRDM1基因两种同源异构体(包含PR结构域的PRDM1α和缺失PR结构域的PRDM1β)表达的影响.方法 以人骨髓瘤细胞系NCI-H929、RPM18226、KM3和LP-1细胞作为研究对象,采用实时定量RT-PCR方法 检测低剂量2ME2(终浓度0.5μmoL/L)作用前后PRDM1α和PRDM1β的表达情况.结果 0.5μmoVL2ME2处理后.在4个MM细胞系中均出现PRDM1基因表达上调,两种同源异构体的表达水平随着2ME2作用时间的延长均有不同程度的增加,并且PRDM1α/PRDM1β比值显著上升,在NCI-H929细胞PRDM1α/PRDM1β比值由基础值1.461±0.033上升至作用72 h时的2.663±0.381(P<0.01),RPMl8226细胞由1.929±0.334上升至2.727±0.362(P<0.05)、KM3细胞由1.471±0.012上升至4.367±0.243(P<0.01)、LP-1细胞由1.660±0.042上升至3.059±0.167(P<0.01).结论 低剂量2ME2诱导骨髓瘤细胞发生分化的同时上调PRDM1α和PRDM1β的表达,但是具有潜在抑癌作用的PRDM1α上调程度更加显著,因而PRDM1α/PRDM1β比值随着2ME2作用时间的延长显著上升,与细胞分化程度呈正相关,并且与PRDM基因家族的正、负作用机制相符合.

abstractsObjective To investigate the effects of low-dose 2-methoxyestradiol(2ME2) on the ex-pression of two isoforms of PRDM1 gene (PRDM1α with and PRDM1β without PR-domain) during the myelo-ma cell differentiation. Methods In myeloma cell line NCI-H929, RPMI8226, KM3 and LP-1, PRDM1α and PRDM1β transcripts were detected by real-time quantitative PCR after treatment with low-dose of 2ME2 (0.5 μmol/L) for 0 h, 48 h and 72 h. Results Both PRDM1α and PRDM1β were time-dependently up-regulated, and the PRDM1α/β ratio was elevated from 1.461±0.033 to 2.663±0.381 (P < 0.01), 1.929±0.334 to 2.727±0.362(P<0.05), 1.471±0.012 to 4.367±0.243(P<0.01) and 1.660±0.042 to 3.059±0.167(P < 0.01) in NCI-H929, RPMI8226, KM3 and LP-1 cells respectively. Conclusion Low dose of 2ME2 can induce differentiation of myeloma cells as well as up-regulate the expression of PRDM1α and PRDM1β in these cells. Elevation of PRDM1α/β ratio was in a time-dependent manner and positively associated with cell differentiation and in accordance with Ying-Yang mechanism of PR-domain-containing gene family.