Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer
Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer
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DOI：
10.1007/s00432-010-0890-z
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Hasan, Qurratulain
中科院分区：
文献类型：
--
作者：
Shetty, Preetha J.;Movva, Sireesha;Hasan, Qurratulain
乳腺癌是全世界妇女癌症死亡的主要原因之一。表观遗传学作为一种以组织特异性方式改变基因表达的独特机制，已成为癌症病理生理学中的重要机制。本研究旨在评估甲基化在调节胰岛素样生长因子2 （IGF2）转录和蛋白表达中的作用，IGF2是一种具有亲代印记的致癌基因。采用石蜡包埋的乳腺档案肿瘤及邻近正常组织标本，进行基于PCR的甲基化检测、基因组PCR、免疫组织化学和实时逆转录酶PCR。与正常组织相比，乳腺癌组织中IGF2外显子9 CpG簇的甲基化显著缺失（P < 0.0001）。免疫组织化学显示IGF2的表达与特异性CpG的低甲基化相关，平均增加两倍。实时RT PCR显示肿瘤组织中转录物增加，支持免疫组化和甲基化结果。共有33%的ApaI IGF2多态性杂合的肿瘤样本由于印迹缺失而表现出双等位基因的IGF2表达；这在任何正常乳腺组织中都没有发现。外显子CpG甲基化改变在乳腺肿瘤中IGF2转录/表达增强中起重要作用。外显子9 CpG的甲基化分析可以作为乳腺肿瘤组织中IGF2上调的生物标志物，并可能在未来发展为一种诊断测试。
Breast Cancer is one of the leading causes of cancer deaths among women worldwide. The role of epigenetics as a distinct mechanism to alter gene expression in a tissue-specific manner has emerged as an important mechanism in the pathophysiology of cancer. Present study was carried out to assess the role of methylation in regulating transcription and protein expression of Insulin-like growth factor 2 (IGF2), an oncogene with parental imprinting.Paraffin-embedded archival breast tumor and adjacent normal tissue samples were used for carrying out PCR-based methylation assay, genomic PCR, immunohistochemistry and Real-Time Reverse transcriptase PCR.A significant loss of methylation in exon 9 CpG cluster of IGF2 in breast tumor tissues was observed when compared to normal tissue (P < 0.0001). Expression of IGF2 by immunohistochemistry exhibited a mean twofold increase correlating with the hypomethylation of this specific CpG. Real-Time RT PCR showed increased transcripts in the tumor tissue supporting the IHC and methylation results. A total of 33% of tumor samples heterozygous for the ApaI IGF2 polymorphism exhibited biallelic IGF2 expression due to loss of imprinting; this was not seen in any of the normal breast tissues.Altered methylation of exonic CpG plays an important role in the enhanced transcription/expression of IGF2 in breast tumors. Methylation analysis of exon 9 CpG can be used as a biomarker for upregulation of IGF2 in breast tumor tissue and maybe developed as a diagnostic test in future.