Oncogenic role of DDX3 in breast cancer biogenesis

被引：179

作者：

Botlagunta, M. ^{[1
]}

Vesuna, F. ^{[1
]}

Mironchik, Y. ^{[1
]}

Raman, A. ^{[2
]}

Lisok, A. ^{[1
]}

Winnard, P., Jr. ^{[1
]}

Mukadam, S. ^{[1
]}

Van Diest, P. ^{[3
]}

Chen, J. H. ^{[4
]}

Farabaugh, P.

Patel, A. H. ^{[5
]}

Raman, V. ^{[6
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA

[2] Univ Maryland, Dept Biol, Baltimore, MD 21201 USA

[3] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[4] Tzu Chi Univ, Dept Life Sci, Hualien, Taiwan

[5] Arvind Patel Inst Virol, Glasgow G11, Lanark, Scotland

[6] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

来源：

ONCOGENE | 2008年 / 27卷 / 28期

基金：

英国医学研究理事会;

关键词：

DDX3; breast cancer; BPDE;

D O I：

10.1038/onc.2008.33

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：

Benzo[a] pyrene diol epoxide (BPDE), the active metabolite of benzo[a] pyrene present in tobacco smoke, is a major cancer-causing compound. To evaluate the effects of BPDE on human breast epithelial cells, we exposed an immortalized human breast cell line, MCF 10A, to BPDE and characterized the gene expression pattern. Of the differential genes expressed, we found consistent activation of DDX3, a member of the DEAD box RNA helicase family. Overexpression of DDX3 in MCF 10A cells induced an epithelial-mesenchymal- like transformation, exhibited increased motility and invasive properties, and formed colonies in soft-agar assays. Besides the altered phenotype, MCF 10A-DDX3 cells repressed E-cadherin expression as demonstrated by both immunoblots and by E-cadherin promoter-reporter assays. In addition, an in vivo association of DDX3 and the E-cadherin promoter was demonstrated by chromatin immunoprecipitation assays. Collectively, these results demonstrate that the activation of DDX3 by BPDE, can promote growth, proliferation and neoplastic transformation of breast epithelial cells.

引用

页码：3912 / 3922

页数：11

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