人肝癌中IGF-2表达与基因印迹异常调控的关系

目的研究人肝癌（ＨＣＣ）中ＩＧＦ－２表达特性及与其“基因印迹”状态变化的关系。方法采用Ｎｏｒｔｈｅｒｎｂｌｏｔ、限制性片段长度多态性（ＲＦＬＰ）结合ＰＣＲ、ＲＰＡ等方法对１７例ＨＣＣ和６例ＨＣＣ细胞系进行了ＩＧＦ－２基因表达，启动子特异性等位基因的表达和ＩＧＦ－２“基因印迹”状态变化的研究。结果ＨＣＣ中ＩＧＦ－２表达为多样性（低表达，近似正常表达和过度表达）和胚胎性（启动子Ｐ３、Ｐ４重新活化和表达）；１例ＨＣＣ中ＩＧＦ－２双等位基因表达来自于Ｐ３“基因印迹”的丢失。结论在ＩＧＦ－２过度表达的ＨＣＣ中存在功能性的ＩＧＦ－２启动子特异性的“基因印迹”丢失现象。ＩＧＦ－２异常表达与其启动子调控失序有关。

Disrupted Regulation of the Genomic Imprinting of IGF2 Gene in Human HCCs

Purpose To study the relationship between the expression patterns of IGF2 gene and their genomic imprinting status in human HCC. Methods Northern blot,RFLP in combination with RTPCR,as well as the RNase protection assay were used to analyze the expression level and patterns of IGF2 gene and the imprinting status of the promoter specific alleles of IGF2 gene in 17 cases of human HCC and 6 HCC cell lines. Results The expression pattern of IGF2 is quite variable among the various HCCs:polymorphic expression (low or undetectable level expression to overexpression) and fetal expression (IGF2 promoter P3 and P4 reactivated and expressed).The true functional loss of promoter specific imprinting (LOI) of IGF2 gene was observed in one IGF2 overexpressing HCC case. Conclusions The abnormal expression of IGF2 gene in HCCs is related to the disrupted IGF2 promoter control. It is supposed that the change of the promoter specific alleles usage might involve in the abbrent expression of IGF2 gene in human HCCs.