Gupta Anu, Kessler Patricia, Rawwas Jawhar, Williams Bryan R G
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Exp Cell Res. 2008 Dec 10;314(20):3663-8. doi: 10.1016/j.yexcr.2008.09.029. Epub 2008 Oct 14.
Cellular retinoic acid binding protein II (CRABP-II) is overexpressed in a wide variety of cancers. Previously we have shown that CRABP-II expression levels are also elevated in neuroblastoma and Wilms tumors. To elucidate the molecular mechanisms underlying the abnormal expression of CRABP-II in Wilms tumor, we studied the expression of MycN and CRABP-II in these tumor samples. Our data revealed that CRABP-II is overexpressed in Wilms tumor compared to normal adjacent non-neoplastic tissue and its levels are even higher in late stage tumors. Its expression correlates with MycN expression in tumors. The tumors that do not express MycN have no CRABP-II expression. The expression of CRABP-II is also regulated by methylation and its promoter is unmethylated in tumors. Knockdown of MycN by small interfering RNA leads to downregulation of CRABP-II. Thus our results suggest that both MycN and DNA methylation are responsible for CRABP-II expression in pediatric tumors and demethylation of CRABP-II may be an early event in tumor development.
细胞视黄酸结合蛋白II（CRABP-II）在多种癌症中过表达。此前我们已表明，神经母细胞瘤和肾母细胞瘤中CRABP-II的表达水平也会升高。为阐明肾母细胞瘤中CRABP-II异常表达的分子机制，我们研究了这些肿瘤样本中MycN和CRABP-II的表达情况。我们的数据显示，与相邻正常非肿瘤组织相比，肾母细胞瘤中CRABP-II过表达，且在晚期肿瘤中其水平更高。其表达与肿瘤中MycN的表达相关。不表达MycN的肿瘤无CRABP-II表达。CRABP-II的表达也受甲基化调控，其启动子在肿瘤中未甲基化。用小干扰RNA敲低MycN会导致CRABP-II下调。因此，我们的结果表明，MycN和DNA甲基化均与儿童肿瘤中CRABP-II的表达有关，CRABP-II的去甲基化可能是肿瘤发生的早期事件。
