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编码人类生长抑制肿瘤抑制基因家族的mRNA转录变体在正常组织和肿瘤组织中的表达谱。

Expression profiles of mRNA transcript variants encoding the human inhibitor of growth tumor suppressor gene family in normal and neoplastic tissues.

作者信息

Walzak Alison A, Veldhoen Nik, Feng Xiaolan, Riabowol Karl, Helbing Caren C

机构信息

Department of Biochemistry and Microbiology, PO Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia, Canada V8W 3P6.

出版信息

Exp Cell Res. 2008 Jan 15;314(2):273-85. doi: 10.1016/j.yexcr.2007.07.029. Epub 2007 Aug 2.

Abstract

The INhibitor of Growth (ING) tumor suppressor gene family is important in regulating cell fate and reads the epigenetic code by interacting specifically with methylated histone H3. Several transcript variants are expressed from the five ING genes but nomenclature for these variants are not consistent in the literature, and very little is known regarding transcript variant expression in normal human tissues and during development. Here we propose a standardized nomenclature for human ING gene family transcript variants and present an expression analysis using real-time quantitative PCR. We establish the steady-state levels of eleven human ING mRNA transcript variants across several fetal, adult, and tumor tissues as well as in cancer-derived cell lines. Consistent with their roles as type II tumor suppressors, we find up to 10,000-fold reduction in many transcript variants in a subset of neoplastic cells. We also find considerable variation in expression levels in different tissues, with up to 1 million-fold higher expression of some ING transcripts in adult, compared to fetal counterparts, particularly in the brain cerebral cortex. These results show differential expression of specific subsets of ING1-5 transcript variants in tissues that may influence the degree to which these variants contribute to epigenetic regulation in cancer and development.

摘要

生长抑制因子(ING)肿瘤抑制基因家族在调节细胞命运以及通过与甲基化组蛋白H3特异性相互作用来解读表观遗传密码方面具有重要作用。五个ING基因表达了几种转录变体,但这些变体的命名在文献中并不一致,而且对于正常人体组织和发育过程中转录变体的表达情况知之甚少。在此,我们提出了一种人类ING基因家族转录变体的标准化命名法,并通过实时定量PCR进行了表达分析。我们确定了十一种人类ING mRNA转录变体在多个胎儿、成人及肿瘤组织以及癌症衍生细胞系中的稳态水平。与它们作为II型肿瘤抑制因子的作用一致,我们发现在一部分肿瘤细胞中,许多转录变体的表达水平降低了多达10000倍。我们还发现不同组织中的表达水平存在显著差异,与胎儿组织相比,某些ING转录本在成人组织中的表达水平高出多达100万倍,尤其是在大脑皮层。这些结果表明,ING1 - 5转录变体的特定子集在组织中的差异表达可能会影响这些变体在癌症和发育过程中对表观遗传调控的贡献程度。

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