Taniguchi T, Schofield A E, Scarlett J L, Morison I M, Sullivan M J, Reeve A E
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Oncogene. 1995 Aug 17;11(4):751-6.
The specificity of IGF2 promoter imprinting was examined in embryonal tissues and Wilms tumour. In several fetal tissues of approximately 12 weeks gestation, IGF2 was found to be monoallelically expressed from all IGF2 promoters i.e. P1, P2, P3 and P4. However, in tissues of slightly older gestation age (15-17 weeks) relaxation of imprinting at the P1 promoter was evident, although the P2-P4 promoters remained imprinted. These data indicate that early in embryogenesis a population of cells exists in which all IGF2 promoters are imprinted, but that as development proceeds the imprinting of the P1 promoter is relaxed. The pattern of IGF2 promoter imprinting was also analysed in Wilms tumour. In some tumours, the pattern of promoter imprinting was identical to that found in early fetal kidney, indicating that this tumour originates within early embryonic kidney tissue. In contrast, in tumours in which relaxation of imprinting had occurred, imprinting relaxation affected all IGF2 promoters. This aberrant pattern of promoter imprinting, which was not detected in fetal kidney, provides further evidence that pathological relaxation of IGF2 imprinting is involved in the genesis of Wilms tumour.
在胚胎组织和肾母细胞瘤中检测了IGF2启动子印记的特异性。在妊娠约12周的几种胎儿组织中，发现IGF2从所有IGF2启动子即P1、P2、P3和P4单等位基因表达。然而，在妊娠年龄稍大（15 - 17周）的组织中，P1启动子的印记松弛明显，尽管P2 - P4启动子仍保持印记。这些数据表明，在胚胎发生早期存在一群细胞，其中所有IGF2启动子都有印记，但随着发育进行，P1启动子的印记松弛。还在肾母细胞瘤中分析了IGF2启动子印记模式。在一些肿瘤中，启动子印记模式与早期胎儿肾脏中的相同，表明这种肿瘤起源于早期胚胎肾脏组织。相反，在发生印记松弛的肿瘤中，印记松弛影响所有IGF2启动子。这种在胎儿肾脏中未检测到的异常启动子印记模式，进一步证明IGF2印记的病理性松弛参与了肾母细胞瘤的发生。
