He L, Cui H, Walsh C, Mattsson R, Lin W, Anneren G, Pfeifer-Ohlsson S, Ohlsson R
Department of Animal Development and Genetics, Uppsala University, Sweden.
Oncogene. 1998 Jan 8;16(1):113-9. doi: 10.1038/sj.onc.1201501.
The IGF2 gene, which encodes a growth factor, is subject to genomic imprinting. The frequently observed loss of IGF2 imprinting in a variety of tumors has been suggested to contribute to neoplasia. Since these reports have not documented the imprinting status of IGF2 at the cellular level, it cannot be excluded that the imprinting status might vary within the tumor. The possibility that loss of IGF2 imprinting in neoplastic cells reflects random imprinting patterns, was therefore addressed. We show here that individual cell populations of the JEG-3 choriocarcinoma cell line display heterogenous imprinting patterns of both IGF2 and H19. In addition, a lack of correlation between IGF2 and H19 imprinting status suggests that any regional parental imprint has been functionally lost. This notion is reinforced by the observation that JEG-3 cell subclones display a range of promoter-specific IGF2 allele usage. Moreover, we observed that the imprinting status of H19 and IGF2 were differentially modulated in JEG-3-derived tumors generated in nude mice. The results suggest that allele-specific expression of IGF2 operates in the absence of a parental imprint. Finally, our observations urge caution with respect to the general interpretation of biallelic expression as 'loss of imprinting'.
编码一种生长因子的IGF2基因会发生基因组印记。多种肿瘤中经常观察到的IGF2印记缺失被认为与肿瘤形成有关。由于这些报告未在细胞水平记录IGF2的印记状态，因此不能排除肿瘤内印记状态可能存在差异。因此，研究了肿瘤细胞中IGF2印记缺失反映随机印记模式的可能性。我们在此表明，JEG-3绒毛膜癌细胞系的单个细胞群体显示出IGF2和H19的异质印记模式。此外，IGF2和H19印记状态之间缺乏相关性表明任何区域亲本印记在功能上已经丧失。JEG-3细胞亚克隆显示出一系列启动子特异性IGF2等位基因使用情况的观察结果进一步强化了这一观点。此外，我们观察到在裸鼠中产生的JEG-3衍生肿瘤中，H19和IGF2的印记状态受到不同调节。结果表明，IGF2的等位基因特异性表达在没有亲本印记的情况下发挥作用。最后，我们的观察结果提醒人们在将双等位基因表达普遍解释为“印记缺失”时要谨慎。
