• Open Access

Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF-κB/cyclin D1 pathway and facilitates tumor growth

Authors

  • Shou Liu,

    1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology 1037 Ruoyu Road, Wuhan 430074, PR China;
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  • Wen-Yong Tan,

    1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology 1037 Ruoyu Road, Wuhan 430074, PR China;
    2. Department of Pathology, Hubei Cancer Hospital, 116 South Zuodaoquan Road, Wuhan, 430074, PR China
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  • Qiong-Rong Chen,

    1. Department of Pathology, Hubei Cancer Hospital, 116 South Zuodaoquan Road, Wuhan, 430074, PR China
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  • Xiao-Ping Chen,

    1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology 1037 Ruoyu Road, Wuhan 430074, PR China;
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  • Kang Fu,

    1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology 1037 Ruoyu Road, Wuhan 430074, PR China;
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  • Yan-Ying Zhao,

    1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology 1037 Ruoyu Road, Wuhan 430074, PR China;
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  • Zheng-Wang Chen

    Corresponding author
    1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology 1037 Ruoyu Road, Wuhan 430074, PR China;
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To whom correspondence should be addressed. E-mail: zwchen21@hotmail.com; liushou362229@yahoo.com.cn

Abstract

Recent research indicates that inflammatory factors play important roles in the initiation and progression of cancers, including breast cancer. Daintain/allograft inflammatory factor-1 (AIF-1) is a crucial mediator in the inflammatory response, but it has not yet been reported whether daintain/AIF-1 is involved in the development of breast cancers. In this study, immunohistochemical analysis found strong positive expression of daintain/AIF-1 in breast ductal tumor epithelia, but only weakly positive or negative expression in the adjacent histologically normal ductal epithelia. Then, the effect of daintian/AIF-1 on the proliferation of the breast cancer cell line MDA-MB-231 was explored via transduction of the daintian/AIF-1 gene into the cells, and via inhibition of the expression of daintain/AIF-1 through short interference RNA. The results demonstrated that up-regulation and down-regulation of daintain/AIF-1 expressions promoted and inhibited the proliferation of MDA-MB-231, respectively. More interestingly, daintain/AIF-1 overexpression facilitated tumor growth in female nude mice. Furthermore, we found that daintain/AIF-1 overexpression up-regulated the expression of cyclin D1 and enhanced the transcriptional activity of nuclear factor-kappa B (NF-κB), a regulator of cyclin D1 expression. In contrast, the down-regulation of daintain/AIF-1 expression decreased cyclin D1 expression and inhibited the transcriptional activity of NF-κB. These results strongly suggest that daintain/AIF-1 can promote the growth of breast tumors via activating NF-κB signaling, which consequently up-regulates the expression of cyclin D1, implying that daintain/AIF-1 may be a novel target molecule for the prognosis and therapy of breast cancer. (Cancer Sci 2008; 99: 952–957)

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