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

作     者：LUO Yong HE Da-lin NING Liang SHEN Shu-lin LI Lei LI Xiang 

作者机构：Department of Urology First Hospital of Xi＇an Jiaotong University Xi＇an 710061 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2006年第119卷第9期

页      面：713-718页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：prostate cancer epithelial-mesenchymal transition hypoxia-inducible factor- 1α 

摘      要：Background Hypoxia-inducible factor- 1α （HIF- 1α） 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- 1α 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- 1α over-expression on the EMT in human prostate cancer cells. Methods We selected the appropriate cell line for HIF- 1α 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- 1α 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 HIF- 1α in LNCaP/HIF- 1α was distinctly higher than that in LNCaP/pcDNA3.1 and LNCaP. The cell numbers of LNCaP/HIF- 1α 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/HIF- 1α, whereas the expression of E-cadherin was down-regulated. Conclusions Over-expression of HIF- 1α 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 HIF- 1α in human prostate cancer cell line.