Hypoxia-inducible factor-1α induces the epithelial-mesenchymal transition of human prostatecancer cells

被引:35
|
作者
Luo Yong [1 ]
He Da-lin [1 ]
Ning Liang [1 ]
Shen Shu-lin [1 ]
Li Lei [1 ]
Li Xiang [1 ]
机构
[1] Xi An Jiao Tong Univ, Hosp 1, Dept Urol, Xian 710061, Peoples R China
关键词
prostate cancer; epithelial-mesenchymal transition; hypoxia-inducible factor-1 alpha;
D O I
10.1097/00029330-200605010-00002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Hypoxia-inducible factor-1 alpha (HEF-1 alpha) is a transcriptional factor that could improve the stimulation of angiogenesis and the metabolic adaptation of tumor cells to hypoxia. A recent study showed that HIF-1 alpha could induce colon cancer cells epithelial-mesenchymal transition (EMT). However, no evidence indicates a similar correlation in human prostate cancer cells. This study was designed to evaluate the effect of HIF-1 alpha over-expression on the EMT inhuman prostate cancer cells. Methods We selected the appropriate cell line for HIF-1 alpha induction from those EMT negative prostate cell lines through vimentin gene detection by RT-PCR. As the result, LNCaP cell line is the best one for further experiment. LNCaP cells were transfected with recombinant plasmid pcDNA3.1(-)/HIF-1 alpha and pcDNA3.1(-) control vector by Lipofectamine 2000 system. The positive cell colonies were confirmed by indirect immunofluorescence labeling. Then Transwell polycarbonate filter was used to analyze the invasive potency. The expression of EMT associated proteins, E-cadherin and vimentin, was detected by Western blotting. Results Among four of the EMT negative cell lines, LNCaP was the only one expressed the vimentin gene but not the associated protein. The expression level of FRF-1 alpha in LNCaP/HIF-1 alpha was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. The cell numbers of LNCaP/HIF-1 alpha that penetrated through the Transwell filter were higher than that of LNCaP/pcDNA3.1 and LNCaP. Compared with the LNCaP/pcDNA3.1. and LNCaP cells, the expression of vimentin was up-regulated in LNCaP/HfF-1 alpha, whereas the expression of E-cadherin was down-regulated. Conclusions Over-expression of HIF-1 alpha stimulates the invasion potency of human prostate carcinoma cells through EMT pathway. The expression of E-cadherin and vimentin, playing established roles in EMT, could be regulated by HfF-1 alpha inhuman prostate cancer cell line.
引用
收藏
页码:713 / 718
页数:6
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