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干细胞转录因子 ZFP57 通过诱导 IGF2 的表达促进癌细胞的无锚定生长。

The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells.

机构信息

Department of Stem Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.

Department of Gastroenterologic Surgery, Graduate School of Medical Sciences, Kanazawa University, Ishikawa, Japan.

出版信息

Oncogene. 2015 Feb 5;34(6):752-60. doi: 10.1038/onc.2013.599. Epub 2014 Jan 27.

DOI:10.1038/onc.2013.599
PMID:24469060
Abstract

Several common biological properties between cancer cells and embryonic stem (ES) cells suggest the possibility that some genes expressed in ES cells might have important roles in cancer cell growth. The transcription factor ZFP57 is expressed in self-renewing ES cells and its expression level decreases during ES cell differentiation. This study showed that ZFP57 is involved in the anchorage-independent growth of human fibrosarcoma HT1080 cells in soft agar. ZFP57 overexpression enhanced, whereas knockdown suppressed, HT1080 tumor formation in nude mice. Furthermore, ZFP57 regulates the expression of insulin-like growth factor 2 (IGF2), which has a critical role in ZFP57-induced anchorage-independent growth. ZFP57 also promotes anchorage-independent growth in ES cells and immortal fibroblasts. Finally, immunohistochemical analysis revealed that ZFP57 is overexpressed in human cancer clinical specimens. Taken together, these results suggest that the ES-specific transcription factor ZFP57 is a novel oncogene.

摘要

几种癌细胞和胚胎干细胞(ES 细胞)之间的共同生物学特性表明,一些在 ES 细胞中表达的基因可能在癌细胞生长中具有重要作用。转录因子 ZFP57 在自我更新的 ES 细胞中表达,其表达水平在 ES 细胞分化过程中降低。本研究表明,ZFP57 参与人成纤维肉瘤 HT1080 细胞在软琼脂中的无锚定生长。ZFP57 过表达增强,而敲低则抑制裸鼠中 HT1080 肿瘤的形成。此外,ZFP57 调节胰岛素样生长因子 2(IGF2)的表达,IGF2 在 ZFP57 诱导的无锚定生长中起关键作用。ZFP57 还促进 ES 细胞和永生化成纤维细胞的无锚定生长。最后,免疫组织化学分析显示,ZFP57 在人类癌症临床标本中过表达。总之,这些结果表明,ES 特异性转录因子 ZFP57 是一种新型癌基因。

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