Epigenetic and functional analysis of IGFBP3 and IGFBPrP1 in cellular immortalization

被引：12

作者：

Fridman, Aviva Levine

Rosati, Rita

Li, Qunfang

Tainsky, Michael A.

机构：

[1] Wayne State Univ, Sch Med, Program Mol Biol & Genet, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA

[2] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 357卷 / 03期

关键词：

immortalization; IGFBP3; IGFBP4; IGFBPrP1; DNA methylation; 5-aza-dC; CpG island; epigenetic silencing; interferon;

D O I：

10.1016/j.bbrc.2007.04.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Carcinogenic transformation of a cell requires bypassing senescence and becoming immortalized. A cellular senescence-like phenotype can be induced in immortal Li-Fraumeni syndrome (LFS) cells by treating them with the DNA methyltransferase inhibitor 5-aza-deoxycytidine. Our micro array-based expression profiling studies of spontaneously immortalized LFS cell lines identified genes that may provide the growth advantage required for the cells to become immortal. Several members of the IGFBP superfamily of genes fit the profile of genes involved in immortalization: silenced during immortalization and reactivated by 5-aza-deoxycytidine. Overexpression of IGFBP3 or IGFBPrP1 in the immortal LFS cell lines suppressed cell growth and inhibited colony formation. Both genes have the expression pattern of an epigenetically regulated gene and contain CpG islands suitable for methylation-dependent silencing. Analysis of how IGFBPs regulate immortalization will lead to a better understanding of this process and may lead to novel methods for the prevention and treatment of cancer. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：785 / 791

页数：7

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