Effect of hypoxia inducible factor 1α on the epithelial-mesenchymal transition of human prostate carcinoma cell and its invasion

Hypoxia inducible factor 1 alpha (HIF-1 alpha) is one important factor for transducing signal and inducing hypoxia effects. Previous study has shown the enhanced tumor invasion and metastasis by up-regulating HIF-1a gene expression. Epithelial-mesenchymal transition (EMT) is known to play a crucial role in tumor invasion and metastasis. This study thus investigated the role of HIF-1 alpha in EMT and invasion of human prostate carcinoma cell line PC3. PC3 cells were cultured under hypoxia condition, for observing the morphological alternation. Real-time PCR was employed to detect mRNA level of HIF-1 alpha, while the invasion and migration of PC3 cells were observed by Transwell assay. Protein levels of HIF-1 alpha, E-cadherin and Vimentin were quantified in Western blotting. Under normal condition, PC3 cells had a polygon shape and regular arrangement of cells. Under hypoxia, cells displayed as oval or spindle shape, with loosely connection and irregular distribution. Real-time PCR showed elevated HIF-1 alpha mRNA expression in hypoxic PC3 cells (P<0.05). Western blotting confirmed the elevated expression of HIF-1 alpha and Vimentin, while decreased E-cadherin in those hypoxic PC3 cells, which also had elevated migration/invasion ability. Hypoxia environment may elevate HIF-1 alpha expression in human prostate carcinoma cells, and enhance their morphological changes. The elevated Vimentin and decreased E-cadherin expression all suggested the facilitation of EMT.