Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF-kappaB/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-kappaB), 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-kappaB. These results strongly suggest that daintain/AIF-1 can promote the growth of breast tumors via activating NF-kappaB 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.
Liu
Shou
S
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.
Tan
Wen-Yong
WY
Chen
Qiong-Rong
QR
Chen
Xiao-Ping
XP
Fu
Kang
K
Zhao
Yan-Ying
YY
Chen
Zheng-Wang
ZW
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D016328:NF-kappa B; D019938:Cyclin D1