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

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)